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Relevance to Autism

Several studies have found rare single gene variations in the SHANK3 gene in autism. However, other studies claimed to find no genetic association or rare variations in the SHANK3 gene in autistic patients from Italian IMGSAC and Chinese Han samples. In addition, rare SHANK3 variants have been linked with schizophrenia and the 22q13.3 deletion syndrome.

Molecular Function

Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.
ASD
Positive association
A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3.
ASD
Positive association
A commonly carried genetic variant, rs9616915, in SHANK3 gene is associated with a reduced risk of autism spectrum disorder: replication in a Chine...
ASD
Negative association
Association study of the CNS patterning genes and autism in Han Chinese in Taiwan.
ASD
Negative association
Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities.
ASD
Negative Association
Association study of SHANK3 gene polymorphisms with autism in Chinese Han population.
ASD
Negative Association
Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection.
ASD
Negative association
Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller's dementia infantilis, a rare subtype of autism spectrum dis...
Childhood disintegrative disorder
Developmental regression
Support
SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism.
Support
Refining analyses of copy number variation identifies specific genes associated with developmental delay.
ASD, DD, ID
Support
Phenotypic and functional analysis of SHANK3 stop mutations identified in individuals with ASD and/or ID.
ASD, ID
Support
Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development.
ASD
Support
The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations.
Epilepsy/seizures
Support
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
ID
Support
De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient.
Rett syndrome-like phenotype
DD, autistic features, stereotyped hand movements,
Support
Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.
ASD, SCZ
Support
Genome-wide characteristics of de novo mutations in autism.
ASD
Support
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...
ASD
ID, epilepsy
Support
Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder.
ASD, ID, epilepsy/seizures
Support
Novel de novo SHANK3 mutation in autistic patients.
ASD
Support
Copy number variation analysis in adults with catatonia confirms haploinsufficiency of SHANK3 as a predisposing factor.
ID, catatonia
Support
Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion.
BPD
ID
Support
Whole-genome sequencing of quartet families with autism spectrum disorder.
ASD
Support
Contribution of SHANK3 mutations to autism spectrum disorder.
ASD
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.
ID
Support
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.
Non-syndromic ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD
Speech delay
Highly Cited
Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family.
Recent Recommendation
SHANK3 gene mutations associated with autism facilitate ligand binding to the Shank3 ankyrin repeat region.
ASD
Recent Recommendation
An architectural framework that may lie at the core of the postsynaptic density.
Recent recommendation
Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...
Recent Recommendation
Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-beta-catenin at excitatory synapses.
Recent Recommendation
Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency.
ASD
ID, epilepsy/seizures
Recent recommendation
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.
ASD
Recent Recommendation
Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease.
Recent Recommendation
Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation.
Recent recommendation
Transcriptional and functional complexity of Shank3 provides a molecular framework to understand the phenotypic heterogeneity of SHANK3 causing aut...
Recent Recommendation
ProSAPiP2, a novel postsynaptic density protein that interacts with ProSAP2/Shank3.
Recent recommendation
Shank3 Is Part of a Zinc-Sensitive Signaling System That Regulates Excitatory Synaptic Strength.
Recent Recommendation
Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders.
ASD
Recent Recommendation
The PSD protein ProSAP2/Shank3 displays synapto-nuclear shuttling which is deregulated in a schizophrenia-associated mutation.
Recent Recommendation
Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3.
MR
Recent recommendation
Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons.
Recent Recommendation
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
Recent Recommendation
Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders.
Recent Recommendation
Heterogeneous dysregulation of microRNAs across the autism spectrum.
Recent recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.
SCZ
Recent Recommendation
Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism.
Recent Recommendation
Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.
Recent recommendation
Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits.
Recent Recommendation
22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.
Phelan-McDermid syndrome
MR

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN230R001 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R002 
 frameshift_variant 
 c.3680insG 
 p.Ala1227Glyfs 
 De novo 
  
 Multiplex 
 GEN230R003 
 copy_number_loss 
  
  
  
  
  
 GEN230R004 
 copy_number_gain 
  
  
  
  
  
 GEN230R005 
 missense_variant 
 c.34C>T 
 p.Arg12Cys 
 Familial 
 Maternal 
 Multiplex 
 GEN230R006 
 missense_variant 
 c.593C>G 
 p.Ala198Gly 
 Familial 
 Maternal 
 Multiplex 
 GEN230R007 
 missense_variant 
 c.898C>T 
 p.Arg300Cys 
 Familial 
 Maternal 
 Simplex 
 GEN230R008 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
 Familial 
  
 Unknown 
 GEN230R009 
 missense_variant 
  
 p.Arg1066Leu 
 Familial 
 Maternal 
 Simplex 
 GEN230R010 
 missense_variant 
 c.3692G>A 
 p.Arg1231His 
 Familial 
 Maternal 
 Multiplex 
 GEN230R011 
 missense_variant 
  
 p.Ser1566Gly 
 Familial 
 Paternal 
 Simplex 
 GEN230R012 
 stop_gained 
 c.3349C>T 
 p.Arg1117Ter 
 De novo 
  
 Multiplex 
 GEN230R013 
 missense_variant 
 c.1606C>T 
 p.Arg536Trp 
 De novo 
  
  
 GEN230R014 
 synonymous_variant 
 c.1023G>A 
 p.(=) 
  
  
  
 GEN230R015 
 missense_variant 
 c.1479C>G 
 p.His494Gln 
  
  
  
 GEN230R016 
 synonymous_variant 
 c.1893C>T 
 p.(=) 
  
  
  
 GEN230R017 
 synonymous_variant 
 c.2043C>G 
 p.(=) 
  
  
  
 GEN230R018 
 missense_variant 
 c.2856G>C 
 p.Ser952Thr 
  
  
  
 GEN230R019 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
  
  
  
 GEN230R020 
 synonymous_variant 
 c.3066G>A 
 p.(=) 
  
  
  
 GEN230R021 
 missense_variant 
 c.3401C>A 
 p.Pro1134His 
  
  
  
 GEN230R022 
 synonymous_variant 
 c.3482T>C 
 p.(=) 
  
  
  
 GEN230R023 
 synonymous_variant 
 c.3558G>A 
 p.(=) 
  
  
  
 GEN230R024 
 missense_variant 
 c.962A>G 
 p.Gln321Arg 
 De novo 
  
 Simplex 
 GEN230R025 
 missense_variant 
 c.1022C>T 
 p.Ser341Leu 
 Familial 
 Paternal 
 Simplex 
 GEN230R026 
 missense_variant 
 c.2908G>T 
 p.Ala970Ser 
 Familial 
 Paternal 
 Simplex 
 GEN230R027 
 missense_variant 
 c.3517G>A 
 p.Ala1173Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN230R028 
 missense_variant 
 c.3788C>T 
 p.Pro1263Leu 
 Familial 
 Paternal 
 Simplex 
 GEN230R029 
 missense_variant 
 c.4216C>G 
 p.Leu1406Val 
 Familial 
 Maternal 
 Multiplex 
 GEN230R030 
 missense_variant 
 c.4328T>C 
 p.Met1443Thr 
 Familial 
 Maternal 
 Simplex 
 GEN230R031 
 inframe_deletion 
 Del4358-4372 
 Del of 5 aa 
 Familial 
 Maternal 
 Multiplex 
 GEN230R032 
 missense_variant 
 c.4669G>A 
 p.Gly1557Ser 
 Familial 
 Paternal 
 Simplex 
 GEN230R033 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Familial 
 Paternal 
 Multiplex 
 GEN230R034 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN230R035 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R036 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN230R037 
 copy_number_loss 
  
  
 De novo 
  
 Multiplex 
 GEN230R038 
 missense_variant 
 c.203T>C 
 p.Leu68Pro 
 Familial 
 Paternal 
 Simplex 
 GEN230R039 
 missense_variant 
 c.670G>A 
 p.Ala224Thr 
 Unknown 
  
 Unknown 
 GEN230R040 
 missense_variant 
 c.2161G>A 
 p.Ala721Thr 
 Unknown 
  
 Unknown 
 GEN230R041 
 splice_site_variant 
 c.2265C+1delG 
 p.Ser755SerfsTer1 
 De novo 
  
 Simplex 
 GEN230R042 
 missense_variant 
 c.3893G>A 
 p.Arg1298Lys 
 Familial 
 Maternal 
  
 GEN230R043 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Unknown 
  
 Unknown 
 GEN230R044 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
 Unknown 
  
 Unknown 
 GEN230R045 
 inframe_deletion 
 c.1320_1338del18 
 p.delGlyProGlyProAlaPro 
 Familial 
 Maternal 
  
 GEN230R046 
 missense_variant 
 c.1967G>A 
 p.Arg656His 
 Familial 
 Paternal 
  
 GEN230R047 
 intron_variant 
 N/A 
 N/A 
  
  
  
 GEN230R048 
 intron_variant 
 N/A 
 N/A 
  
  
  
 GEN230R049 
 intron_variant 
 N/A 
 N/A 
 De novo 
  
  
 GEN230R050 
 copy_number_loss 
  
  
 Familial 
 Maternal 
  
 GEN230R051 
 inframe_insertion 
 N/A 
 N/A 
  
  
  
 GEN230R052 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
  
  
  
 GEN230R053 
 missense_variant 
 c.3517G>A 
 p.Ala1173Thr 
  
  
  
 GEN230R054 
 missense_variant 
 c.3788G>T 
 p.Pro1263Leu 
  
  
  
 GEN230R055 
 synonymous_variant 
 c.750C>T 
 p.(=) 
  
  
  
 GEN230R056 
 synonymous_variant 
 c.1563G>A 
 p.(=) 
  
  
  
 GEN230R057 
 synonymous_variant 
 c.4446G>A 
 p.(=) 
  
  
  
 GEN230R058 
 synonymous_variant 
 c.4908C>T 
 p.(=) 
  
  
  
 GEN230R059 
 synonymous_variant 
 c.4935C>T 
 p.(=) 
  
  
  
 GEN230R060 
 synonymous_variant 
 c.483C>T 
 p.(=) 
  
  
  
 GEN230R061 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R062 
 copy_number_loss 
  
  
  
  
  
 GEN230R063 
 copy_number_loss 
  
  
  
  
  
 GEN230R064 
 copy_number_loss 
  
  
  
  
  
 GEN230R065 
 copy_number_loss 
  
  
  
  
  
 GEN230R066 
 copy_number_loss 
  
  
  
  
  
 GEN230R067 
 copy_number_loss 
  
  
  
  
  
 GEN230R068 
 copy_number_loss 
  
  
  
  
  
 GEN230R069 
 copy_number_loss 
  
  
  
  
  
 GEN230R070 
 copy_number_loss 
  
  
  
  
  
 GEN230R071 
 copy_number_loss 
  
  
  
  
  
 GEN230R072 
 copy_number_loss 
  
  
  
  
  
 GEN230R073 
 copy_number_loss 
  
  
  
  
  
 GEN230R074 
 copy_number_loss 
  
  
  
  
  
 GEN230R075 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
  
  
  
 GEN230R076 
 missense_variant 
 c.2161G>A 
 p.Ala721Thr 
  
  
  
 GEN230R077 
 synonymous_variant 
 c.2310G>A 
 p.(=) 
  
  
  
 GEN230R078 
 synonymous_variant 
 c.2997C>T 
 p.(=) 
  
  
  
 GEN230R079 
 synonymous_variant 
 c.3363C>T 
 p.(=) 
  
  
  
 GEN230R080 
 missense_variant 
 c.3999T>G 
 p.Val1333Gly 
  
  
  
 GEN230R081 
 synonymous_variant 
 c.4947C>T 
 p.(=) 
  
  
  
 GEN230R082 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
  
  
  
 GEN230R083 
 missense_variant 
 c.3581G>A 
 p.Gly1194Asp 
 Unknown 
  
 Simplex 
 GEN230R084 
 missense_variant 
 c.3715A>T 
 p.Ser1239Cys 
 Unknown 
  
 Simplex 
 GEN230R085 
 missense_variant 
 c.3893G>A 
 p.Arg1298Lys 
 Unknown 
  
 Simplex 
 GEN230R086 
 missense_variant 
 c.4018G>A 
 p.Ala1340Thr 
 Unknown 
  
 Simplex 
 GEN230R087 
 missense_variant 
 c.4621C>T 
 p.Pro1541Ser 
 Unknown 
  
 Simplex 
 GEN230R088 
 missense_variant 
 c.4673C>T 
 p.Ala1558Val 
 Unknown 
  
 Simplex 
 GEN230R089 
 missense_variant 
 c.4778A>T 
 p.Thr1593Ile 
 Unknown 
  
 Simplex 
 GEN230R090 
 missense_variant 
 c.4856G>A 
 p.Arg1619His 
 Unknown 
 Not paternal 
 Simplex 
 GEN230R091 
 missense_variant 
 c.4873A>T 
 p.Pro1625Ser 
 Unknown 
  
 Simplex 
 GEN230R092 
 missense_variant 
 c.4877C>T 
 p.Ser1626Lys 
 Unknown 
  
 Simplex 
 GEN230R093 
 missense_variant 
 c.4894G>A 
 p.Ala1632Thr 
 Unknown 
 Not paternal 
 Simplex 
 GEN230R094 
 missense_variant 
 c.4913G>A 
 p.Gly1638Asp 
 Unknown 
  
 Simplex 
 GEN230R095 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Unknown 
  
 Simplex 
 GEN230R096 
 synonymous_variant 
 c.522C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R097 
 missense_variant 
 c.612C>A 
 p.Asp204Glu 
  
  
 Multiplex 
 GEN230R098 
 missense_variant 
 c.763C>T 
 p.His255Tyr 
  
  
 Multiplex 
 GEN230R099 
 intron_variant 
 c.769-7C>G 
  
  
  
 Multiplex 
 GEN230R100 
 missense_variant 
 c.898C>T 
 p.Arg300Cys 
  
  
 Multiplex 
 GEN230R101 
 missense_variant 
 c.920C>G 
 p.Ala307Gly 
  
  
 Multiplex 
 GEN230R102 
 intron_variant 
 c.1031-14C>T 
  
  
  
 Multiplex 
 GEN230R103 
 synonymous_variant 
 c.1254G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R104 
 missense_variant 
 c.1315C>T 
 p.Pro439Ser 
  
  
 Multiplex 
 GEN230R105 
 synonymous_variant 
 c.1335G>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R106 
 missense_variant 
 c.1337G>T 
 p.Gly446Val 
  
  
 Multiplex 
 GEN230R107 
 intron_variant 
 c.2077+10C>A 
  
  
  
 Multiplex 
 GEN230R108 
 intron_variant 
 c.2313+20G>A 
  
  
  
 Multiplex 
 GEN230R109 
 intron_variant 
 c.2398+11G>A 
  
  
  
 Multiplex 
 GEN230R110 
 synonymous_variant 
 c.249G>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R111 
 synonymous_variant 
 c.3360C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R112 
 synonymous_variant 
 c.3708G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R113 
 missense_variant 
 c.3761C>T 
 p.Ala1254Val 
  
  
 Multiplex 
 GEN230R114 
 missense_variant 
 c.3764C>T 
 p.Pro1255Leu 
  
  
 Multiplex 
 GEN230R115 
 synonymous_variant 
 c.3765G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R116 
 missense_variant 
 c.3836C>T 
 p.Pro1279Leu 
  
  
 Multiplex 
 GEN230R117 
 missense_variant 
 c.4025C>T 
 p.Pro1342Leu 
  
  
 Multiplex 
 GEN230R118 
 synonymous_variant 
 c.4050C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R119 
 synonymous_variant 
 c.4368C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R120 
 missense_variant 
 c.4405G>C 
 p.Gly1469Arg 
  
  
 Multiplex 
 GEN230R121 
 missense_variant 
 c.4406G>T 
 p.Gly1469Val 
  
  
 Multiplex 
 GEN230R122 
 synonymous_variant 
 c.4479C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R123 
 missense_variant 
 c.4490G>A 
 p.Arg1497Gln 
  
  
 Multiplex 
 GEN230R124 
 synonymous_variant 
 c.4641C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R125 
 missense_variant 
 c.4720G>A 
 p.Gly1574Arg 
  
  
 Multiplex 
 GEN230R126 
 synonymous_variant 
 c.5106C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R127 
 splice_site_variant 
 del(G) 
 Splice-site 
 De novo 
  
  
 GEN230R128 
 missense_variant 
 c.1606C>T 
 p.Arg536Trp 
 De novo 
  
  
 GEN230R129 
 stop_gained 
 c.3349C>T 
 p.Arg1117Ter 
 De novo 
  
  
 GEN230R130 
 frameshift_variant 
 c.1339_1340insG 
 p.Ala447GlyfsTer57 
 Familial 
 Maternal 
  
 GEN230R131 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R132 
 frameshift_variant 
 c.1339_1340insG 
 p.Ala447fsTer503 
 Familial 
 Paternal 
 Possible multi-generational 
 GEN230R133 
 frameshift_variant 
 c.3931delG 
 p.Glu1311fsTer1401 
 Unknown (not maternal) 
  
  
 GEN230R134 
 missense_variant 
 c.421C>G 
 p.Pro141Ala 
 De novo 
  
  
 GEN230R135 
 splice_site_variant 
 c.1820-4G>A 
  
 Familial 
 Maternal 
  
 GEN230R136 
 missense_variant 
 c.4402G>T 
 p.Ala1468Ser 
 Unknown 
  
  
 GEN230R137 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R138 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R139 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R140 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R141 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R142 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R143 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R144 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R145 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R146 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R147 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R148 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R149 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R150 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R151 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R152 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R153 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R154 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R155 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R156 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R157 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R158 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R159 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R160 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R161 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R162 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R163 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R164 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R165 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R166 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R167 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R168 
 frameshift_variant 
 c.2497delG 
 p.Pro834ArgfsTer59 
 De novo 
  
  
 GEN230R169 
 stop_gained 
 c.1527G>A 
 p.Trp509Ter 
 De novo 
  
  
 GEN230R170 
 missense_variant 
 c.3169C>T 
 p.Leu1057Phe 
 Unknown 
  
 Unknown 
 GEN230R171 
 stop_gained 
 c.2425G>T 
 p.Glu809Ter 
 De novo 
  
 Simplex 
 GEN230R172 
 frameshift_variant 
 delCCCTG 
 p.Ala1076GlufsTer218 
 De novo 
  
 Simplex 
 GEN230R173 
 frameshift_variant 
 delCT 
 p.Leu1142ValfsTer153 
 De novo 
  
 Simplex 
 GEN230R174 
 frameshift_variant 
 delCCCT 
 p.Ser1202CysfsTer81 
 De novo 
  
 Simplex 
 GEN230R175 
 frameshift_variant 
 delGGGCCCAGCCCCC 
 p.Arg1255LeufsTer25 
 De novo 
  
 Simplex 
 GEN230R176 
 frameshift_variant 
 insGGCCA 
 p.Gly1271AlafsTer15 
 De novo 
  
 Simplex 
 GEN230R177 
 stop_gained 
 c.3727C>T 
 p.Gln1243Ter 
 De novo 
  
 Simplex 
 GEN230R178 
 frameshift_variant 
 delC 
 p.Pro1005ArgfsTer73 
 Unknown 
 Not maternal 
 Simplex 
 GEN230R179 
 frameshift_variant 
 delAG 
 p.Gly1339GlufsTer5 
 Unknown 
 Not maternal 
 Simplex 
 GEN230R180 
 inframe_deletion 
 delCCCGGCCCCGCG 
 p.Pro442_Ala445del 
 Unknown 
  
 Unknown 
 GEN230R181 
 missense_variant 
 c.1682C>T 
 p.Ser561Leu 
 Unknown 
  
 Unknown 
 GEN230R182 
 missense_variant 
 c.2254G>A 
 p.Ala752Thr 
 Unknown 
  
 Unknown 
 GEN230R183 
 missense_variant 
 c.2685T>C 
 p.Leu895Pro 
 Unknown 
  
 Unknown 
 GEN230R184 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
 Unknown 
  
 Unknown 
 GEN230R185 
 missense_variant 
 c.3704C>A 
 p.Pro1235Gln 
 Unknown 
  
 Unknown 
 GEN230R186 
 missense_variant 
 c.3796G>A 
 p.Ala1266Thr 
 Unknown 
  
 Unknown 
 GEN230R187 
 missense_variant 
 c.3825A>T 
 p.Glu1275Asp 
 Unknown 
  
 Unknown 
 GEN230R188 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R189 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R190 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R191 
 stop_gained 
 c.1485G>A 
 p.Trp495Ter 
 De novo 
  
 Simplex 
 GEN230R192 
 frameshift_variant 
 c.1834_1835insGG 
 p.Thr612fs 
 Familial 
 Paternal 
 Multiplex 
 GEN230R193 
 missense_variant 
 c.2027G>A 
 p.Arg676His 
 Familial 
 Paternal 
 Simplex 
 GEN230R194 
 missense_variant 
 c.3866C>T 
 p.Pro1289Leu 
 Familial 
 Maternal 
 Simplex 
 GEN230R195 
 missense_variant 
 c.3869C>T 
 p.Ala1290Val 
 Familial 
 Maternal 
 Simplex 
 GEN230R196 
 stop_gained 
 c.1575C>A 
 p.Cys525Ter 
 Unknown 
  
 Unknown 
 GEN230R197 
 missense_variant 
 c.920C>G 
 p.Ala307Gly 
 Unknown 
  
 Unknown 
 GEN230R198 
 missense_variant 
 c.985T>A 
 p.Phe329Ile 
 Unknown 
  
 Unknown 
 GEN230R199 
 missense_variant 
 c.2024G>A 
 p.Arg675Gln 
 Unknown 
  
 Unknown 
 GEN230R200 
 missense_variant 
 c.4391G>A 
 p.Arg1464His 
 Unknown 
  
 Unknown 
 GEN230R201 
 missense_variant 
 c.2060G>T 
 p.Ser687Ile 
 Unknown 
  
 Unknown 
 GEN230R202 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN230R203 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R204 
 frameshift_variant 
 c.925_926delAG 
 p.Arg309GlyfsTer21 
 De novo 
  
 Multiplex 
 GEN230R205 
 frameshift_variant 
 c.3259delC 
 p.Ser1088ProfsTer6 
 De novo 
  
 Multiplex 
 GEN230R206 
 frameshift_variant 
 c.2955_2970dup 
 p.Pro992ArgfsTer325 
 De novo 
  
 Simplex 
 GEN230R207 
 frameshift_variant 
 c.3100delC 
 p.Ala1034fsTer44 
 De novo 
  
 Simplex 
 GEN230R208 
 stop_gained 
 c.5008A>T 
 p.Lys1670Ter 
 Unknown 
 Not maternal 
  
 GEN230R209 
 copy_number_loss 
  
  
 Unknown 
 Not maternal 
  
 GEN230R210 
 missense_variant 
 c.3598G>C 
 p.Ala1200Pro 
 De novo 
  
 Simplex 
 GEN230R211 
 frameshift_variant 
 c.3727dup 
 p.Ala1243fs 
 De novo 
  
  
 GEN230R212 
 frameshift_variant 
 insG 
  
 De novo 
  
 Simplex 
 GEN230R213 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R214 
 copy_number_loss 
  
  
 Unknown 
  
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN230C001 
 intron_variant 
 rs76224556 
 c.1304+48C>T 
  
 Case cohort of 221 ASD patients (133 from South Caroline Autism Project/SCAP, 88 from Italy); control cohort of 982 individuals 
 Discovery 
 GEN230C002 
 missense_variant 
 rs9616915 
 c.734T>C 
 p.Ile245Thr 
 Case cohort of 212 ASD patients; control cohort of 636 controls (Chinese) 
 Discovery 
 GEN230C003 
 intron_variant 
 rs5770820 
 c.2134+407G>A 
  
 Simons Simplex Collection (SSC) GWAS dataset consisting of 2591 simplex ASD families 
 Discovery 



Model Summary

Specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions in Shank3 heterozygous mice.

External Links

AllenBrainAtlas   MGI Logo  Entrez Gene

References

Type
Title
Author, Year
Primary
Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication.
Additional
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
Additional
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.
Additional
Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.
Additional
Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.
Additional
Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.
Additional
Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission.
Additional
Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators.
Additional
Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits.
Additional
Cerebellar associative sensory learning defects in five mouse autism models.
Additional
Altered Striatal Synaptic Function and Abnormal Behaviour in Shank3 Exon4-9 Deletion Mouse Model of Autism.
Additional
Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects.
Additional
CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency.
Additional
Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.
Additional
Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs.

SHANK3_1_CN_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted Cre/loxP mediated deletion of exon 4 to exon 9 of Shank3 gene.
Allele Type: Targeted (Conditional)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Bruce4 C57BL/6
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_2_CN_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted Cre/loxP mediated deletion of exon 4 to exon 9 of Shank3 gene.
Allele Type: Targeted (Conditional)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Bruce4 C57BL/6
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_4_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination mediated replacement of exon 13 to 16's containing the PDZ domain of Shank3 gene
Allele Type: Targeted (knockout)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_5_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination mediated replacement of exons 4 - 7 containing the ankyrin repeat domains of Shank3 gene
Allele Type: Targeted (knockout)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_6_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conventional gene-targeting approach to delete exons 4-9 of Shank3 gene
Allele Type: Targeted (knockout)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: 129SvEv
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_3_CN_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Conditional deletion of exon 21 of Shank3 resulting in lack of entire C-termain portion of Shank3 (the article reporting this model was retracted)
Allele Type: Targeted (Conditional)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

SHANK3_7_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination mediated deletion of exon 11 within the SH3 domain of Shank3 gene
Allele Type: Targeted (knockout)
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified

SHANK3_8_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 21 of the Shank3 gene was floxed using a neo cassette (frt flanked). Mice containing the floxed gene were mated to actin-Cre mice for deleting the exon. Wild type Shank3 protein is not detected in these mice. Lower molecular weight isoforms of Shank3 are however detectable.
Allele Type: Targeted (knockout)
Strain of Origin: 129S6/SvEvTac
Genetic Background: C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

SHANK3_9_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Exon 21 of the Shank3 gene was floxed using a neo cassette (frt flanked). Mice containing one copy of the floxed gene were mated to actin-Cre mice for generating Shank3 hets
Allele Type: Targeted (knockout)
Strain of Origin: 129S6/SvEvTac
Genetic Background: C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

SHANK3_10_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: The autism-associated guanine nucleotide insertion mutation (Shank3G) present in exon 21 was inserted into the Shank 3 gene, with the construct containing the mutation in exon 21 being introduced into intron 20 (developed using site directed mutagenesis and homologous recombination) followed by a a transcriptional STOP(to prevent exon skipping or splicing). The additional G results in a frameshift mutation and a premature stop codon downstream of exon 21. The mice containing the Shank3G mutation were crossed for 4 generations with C57BL6J. Het and homozygous mice were generated as littermates
Allele Type: Targeted(knockin)
Strain of Origin: 129Sv/Evs6
Genetic Background: C57BL/6J*129Sv/Evs6
ES Cell Line: SM-1
Mutant ES Cell Line:
Model Source:

SHANK3_11_KI_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: The autism-associated guanine nucleotide insertion mutation (Shank3G) present in exon 21 was inserted into the Shank 3 gene, with the construct containing the mutation in exon 21 being introduced into intron 20 (developed using site directed mutagenesis and homologous recombination) followed by a a transcriptional STOP(to prevent exon skipping or splicing). The additional G results in a frameshift mutation and a premature stop codon downstream of exon 21. The mice containing the Shank3G mutation were crossed for 4 generations with C57BL6J. Het and homozygous mice were generated as littermates
Allele Type: Targeted(knockin)
Strain of Origin: 129Sv/Evs6
Genetic Background: C57BL/6J*129Sv/Evs6
ES Cell Line: SM-1
Mutant ES Cell Line:
Model Source:

SHANK3_13_cKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exons 4-9 of Shank3 gene containing the ankyrin repeats, were deleted using a Cre-LoxP mediated excision. After germline transmission in C57BL6J, knock in mice were mated with mice expressing Flp1 recombinase to excise the Neo cassette used for positive selection. The resulting conditional Shank3 mice were crossed with mice expressing ZP3-Cre to excise exon4-9 in oocytes of female pups, then further crossed with C57BL6J, to homozygosity (Authors do not note that the construct used or the final mice are the same as that reported used in Bozdagi et al Mol Autism (2010) or Yang et al J Neurosci
Allele Type: Targeted(conditional knockout)
Strain of Origin:
Genetic Background: C57BL6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

SHANK3_14_cKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Exons 4-9 of Shank3 gene containing the ankyrin repeats, were deleted using a Cre-LoxP mediated excision. After germline transmission in C57BL6J, knock in mice were mated with mice expressing Flp1 recombinase to excise the Neo cassette used for positive selection. The resulting conditional Shank3 mice were crossed with mice expressing ZP3-Cre to excise exon4-9 in oocytes of female pups, then further crossed with C57BL6J. (Authors do not note that the construct used or the final mice are the same as that reported used in Bozdagi et al Mol Autism (2010) or Yang et al J Neurosci (2012), even if
Allele Type: Targeted(conditional knockout)
Strain of Origin:
Genetic Background: C57BL6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

SHANK3_15_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: The autism-associated guanine nucleotide insertion mutation (Shank3InsG) was placed at position 3680 in exon 21, this insertion causes a frameshift and a stop codon immediately after the G insertion. The mice were maintained in C57B6/S129Sv background. Mice were bred to homozygosity normally
Allele Type: Targeted(knockin)
Strain of Origin:
Genetic Background: C57BL6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

SHANK3_16_KI_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: The autism-associated guanine nucleotide insertion mutation (Shank3InsG) was placed at position 3680 in exon 21, this insertion causes a frameshift and a stop codon immediately after the G insertion. The mice were maintained in C57B6/S129Sv background
Allele Type: Targeted(knockin)
Strain of Origin:
Genetic Background: C57BL6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

SHANK3_17_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: The schizophrenia associated non-sense mutation chanding arginine to a stop codon (R1117X) was introduced by changing the codon for R 'CGG' to stop codon TGA in position 1117. Mice were maintained in C57Bl6*129Sv background and bred to homozygosity
Allele Type: Targeted(knockin)
Strain of Origin:
Genetic Background: C57BL6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

SHANK3_18_KI_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: The schizophrenia associated non-sense mutation chanding arginine to a stop codon (R1117X) was introduced by changing the codon for R 'CGG' to stop codon TGA in position 1117. Mice were maintained in C57Bl6*129Sv background and bred to homozygosity
Allele Type: Targeted(knockin)
Strain of Origin:
Genetic Background: C57BL6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

SHANK3_8_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Ablation of exon 21 (previously described in PMID 24259569); Deletion of exon 21 removes the majority of the Shank3 C-terminus; major isoforms absent but fast migrating truncated fragments present;
Allele Type: Targeted (knockout)
Strain of Origin:
Genetic Background: C57BL6/J
ES Cell Line:
Mutant ES Cell Line:
Model Source: PMID 24259569

SHANK3_19_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: To disrupt all murine Shank3 isoforms, exons 4-22 of the Shank3 gene were floxed, spanning 58 kb to include the coding sequences for all known Shank3 isoforms. The floxed mice were bred with CMV-cre mice to generate mice with deletions of exons 4-22, bred till homozygosity. Authors report loss of all known Shank3 mRNA and protein
Allele Type: Targeted(knockout)
Strain of Origin:
Genetic Background: C57Bl/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

SHANK3_19_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Shank3 exon 4-22 floxed mice were bred to CMV-cre mice to generate heterozygous Shank3 knockouts
Allele Type: Targeted(knockout)
Strain of Origin:
Genetic Background: C57Bl/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

SHANK3_20_CKO_HM_NAc

Model Type: Genetic
Model Genotype: Homozygous
Mutation: 10-12 week old exon 4-22 floxed, female mice were injected with AAV10- Cre virus bilaterally in the nucleus accumbens (NAc) to selectively knockdown Shank3 in the NAc. Four weeks after the injection electrodes were surgically implanted in the NAc
Allele Type: Targeted(conditional knockout)
Strain of Origin:
Genetic Background: C57Bl/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

SHANK3_4_KO_HT

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination mediated replacement of exon 13 to 16's containing the PDZ domain of Shank3 gene
Allele Type: Targeted (knockout)
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J 8129Sv/Ev
ES Cell Line: R1
Mutant ES Cell Line:
Model Source: PMID 21423165

SHANK3_1_CN_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Protein expression level evidence1
Decreased
Description: Decreased levels of Shank3 protein in postsynaptic density extracts
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
Gene expression1
Decreased
Description: Decreased levels of Shank3 mRNA expression
Exp Paradigm: Shank3 Mrna Expression Levels
 Quantitative PCR (qRT-PCR)
 Unreported
Developmental trajectory1
 No Change
 General observations
 P2-P14
General characteristics1
 No Change
 General observations
 Unreported
Brain morphology1
 No Change
 
 Unreported
Seizures1
 No Change
 
 Unreported
Social approach1
 No Change
 Three-chamber social approach test
 Unreported
Social interaction1
 No Change
 
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Repetitive behavior, Sensory

SHANK3_2_CN_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Structural dendritic plasticity1
Abnormal
Description: Abnormal synaptic potentiation and spine expansion in CA1 neurons
Exp Paradigm: Simultaneous monitoring of spine size and synaptic response in CA1 neurons before and after TBP
 Whole-cell patch clamp
 Unreported
Neuroreceptor activity2
Decreased
Description: Decreased glutamate AMPA receptor component of neuronal sigaling indicated by mean slope of I/O function
Exp Paradigm: Whole cell recordings of hippocampal slices
 Whole-cell patch clamp
 Unreported
Synaptic plasticity1
Decreased
Description: Decreaed maintenance of long-term potentiation at Schaffer collateral/CA1 synapses in response to either high-frequency stimulus or TBS
Exp Paradigm: Extracellular fEPSP recordings at Schaffer collateral/CA1 synapses after induction of LTP by tetanic stimulation or TBS
 Field potential recordings
 Unreported
Synaptic transmission1
Abnormal
Description: Abnormal synaptic transmission demonstrated by decreased amplitude of miniature excitatory postsynaptic currents (mEPSCs) with increased frequency of mEPSCs in hippocampal CA1 pyramidal neurons
Exp Paradigm: Whole cell patch-clamp recordings of spontaneous mEPSCs in the presence of tetrodotoxin in hippocampal CA1 pyramidal neurons
 Whole-cell patch clamp
 3 months
Synaptic transmission1
Decreased
Description: Decreased I/O curves of fEPSP slope vs. stimulus intensity in the presence of NDMA receptor antagonist APV
Exp Paradigm: Extracellular recordings of Schaffer collateral-CA1 synapses in hippocampal slices with addition of NMDA receptor antagonist APV
 Field potential recordings
 3-4 weeks
Presynaptic function: paired-pulse facilitation1
Decreased
Description: Decreased paired-pulse ratio in hippocampal CA1 pyramidal neurons
Exp Paradigm: Whole cell patch-clamp recordingsin the presence of tetrodotoxin in hippocampal CA1 pyramidal neurons
 Whole-cell patch clamp
 3 months
Synaptic plasticity: hippocampal LTP2
Decreased
Description: Decreased long term potentation induced by high-frequency stimulation
Exp Paradigm: Whole cell recordings of hippocampal slices
 Whole-cell patch clamp
 Unreported
Synaptic transmission1
Decreased
Description: Decreased I/O curves of fEPSP slope vs. stimulus intensity
Exp Paradigm: Extracellular recordings of Schaffer collateral-CA1 synapses in hippocampal slices
 Field potential recordings
 3-4 weeks
Social interaction1
Decreased
Description: Decreased male-female social interaction demonstrated by shorter duration of total social sniffing by male
Exp Paradigm: Direct-contacts between male-female mice
 Reciprocal social interaction test
 2.5-4 months
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations during male-female social interaction
Exp Paradigm: Call latency towards unfamiliar female mouse
 Monitoring ultrasonic vocalizations: reciprocal social interaction test: male-female
 2.5-4 months
Protein expression level evidence1
Decreased
Description: Decreased levels of Shank3 protein in postsynaptic density extracts
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
Gene expression1
Decreased
Description: Decreased levels of Shank3 mRNA expression
Exp Paradigm: Shank3 Mrna Expression Levels
 Quantitative PCR (qRT-PCR)
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased GluR1 immunoreactive puncta in neurons
Exp Paradigm: Glur1 Protein Expression
 Western blot
 3 months
Developmental trajectory1
 No Change
 General observations
 P2-P14
General characteristics1
 No Change
 General observations
 Unreported
Brain morphology1
 No Change
 
 Unreported
Synaptic plasticity1
 No Change
 Field potential recordings
 Unreported
Synaptic transmission1
 No Change
 Field potential recordings
 3-4 weeks
Seizures1
 No Change
 
 Unreported
Olfaction1
 No Change
 Olfactory habituation-dishabituation test
 2.5-4 months
Social approach1
 No Change
 Three-chamber social approach test
 Unreported
Social interaction1
 No Change
 
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_4_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain size1
Increased
Description: Increased volumetric enlargement of caudate
Exp Paradigm: Three-Dimensional magnetic resonance imaging of intact brain
 Magnetic resonance imaging (MRI)
 5-6 weeks
Dendritic spine density and architecture1
Increased
Description: Increased dendritic complexity indicative of neuronal hypertrophy due to increased complexity of dendritic arborization, total dendritic length, and surface area
Exp Paradigm: Sholl analysis of golgi stained striatal medium spiny neurons (MSNs)
 Sholl analysis
 5-6 weeks
Dendritic spine density and architecture1
Decreased
Description: Decreased spine density in medium spiny neurons
Exp Paradigm: Lucifer Yellow cell filling of medium spiny neurons (MSNs)
 Histology: lucifer yellow- medium spiny neurons
 5-6 weeks
Post-synaptic density size1
Decreased
Description: Decreased reductikon in mean thickness of Postsynaptic Density (PSD); Decreased PSD length
Exp Paradigm: Electron Microscopy Analysis
 Electron microscopy
 5-6 weeks
Synaptic transmission1
Decreased
Description: Decreased synaptic transmission indicated by reduced field population spikes
Exp Paradigm: Extracellular recordings of cortico-striatal synaptic circuitry in acute brain slices
 Field potential recordings
 6-7 weeks
Synaptic transmission: excitatory1
Abnormal
Description: Abnormal postsynaptic function demonstrated by decreased frequency and amplitude of AMPAR-mEPSCs of MSNs
Exp Paradigm: Whole-cell voltage clamp recordings of AMPAR-mESPCS in dorsolateral striatal medium spiny neurons (MSNs)
 Whole-cell patch clamp
 6-7 weeks
Social interaction1
Decreased
Description: Decreased social interaction behavior demonstrated by clear preference for interacting with empty cage
Exp Paradigm: Modified three-chambered social arena task
 Three-chamber social approach test
 5-6 weeks
Social interaction1
Abnormal
Description: Abnormal social novelty demonstrated by decreased time interacting with novel mouse
Exp Paradigm: Modified three-chambered social arena task with introduction of a novel social partner
 Three-chamber social approach test
 5-6 weeks
Social interaction1
Decreased
Description: Decreased reciprocal interaction, frequency of nose-to-nose interaction and anogenital sniffing
Exp Paradigm: Open Arena test, freely interacting dyadic paris of wild type - mutant mice
 Open field test
 5-6 weeks
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory indicated by development of pronounced skin lesions with varying degrees of penetrance
 
 4-5 months
Anxiety1
Increased
Description: Increased anxiety demonstrated by: reduced rearing activity which is a form of vertical exploration, less time exploring open arms of maze, increased latency to cross brightly lit area
Exp Paradigm: Open field test measurement of rearing; Elevated Zero Maze; Light-Dark emergence test
 Open field test; Light-dark exploration test; Elevated zero maze test
 5-6 weeks
Protein expression level evidence1
Decreased
Description: Decreased levels of SAPAP3, Homer-1b/c, PSD-93, GluR2, NR2A and NR2B in PSD's derived from striatum
Exp Paradigm: Psd Protein Network
 Western blot
 5-6 weeks
Size/growth1
 No Change
 General observations
 Unreported
Object recognition memory1
 No Change
 
 3-6 months
Spatial reference memory1
 No Change
 Morris water maze test
 5-6 weeks
General locomotor activity1
 No Change
 Open field test
 5-6 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 5-6 weeks
Brain anatomy1
 No Change
 Macroscopic analysis; Histology
 5-6 weeks
Brain cytoarchitecture1
 No Change
 Histology: lucifer yellow- medium spiny neurons
 5-6 weeks
Brain size1
 No Change
 Magnetic resonance imaging (MRI)
 5-6 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Field potential recordings
 6-7 weeks
Synaptic transmission2
 No Change
 Field potential recordings
 6-7 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp
 6-7 weeks
Seizures1
 No Change
 General observations
 5-6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_5_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social interaction1
Abnormal
Description: Abnormal social novelty demonstrated by decreased time interacting with novel mouse
Exp Paradigm: Modified three-chambered social arena task with introduction of a novel social partner
 Three-chamber social approach test
 Unreported
Developmental trajectory1
 No Change
 General observations
 3-6 months
Size/growth1
 No Change
 General observations
 Unreported
Anxiety1
 No Change
 Open field test; Light-dark exploration test; Elevated zero maze test
 Unreported
Social interaction1
 No Change
 Three-chamber social approach test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

SHANK3_6_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Decreased locomotion; No Change in time spent moving, rearing, stereotypical activities
Exp Paradigm: Open field test
 Open field test
 Unreported
Motor coordination and balance1
Decreased
Description: Decreased motor coordination demonstrated by increased foot baults, slower movement pace
Exp Paradigm: Foot-misplacement test
 Footslip test
 Unreported
Grip strength1
Decreased
Description: Decreased motor strength demonstrated by delayed climbing and abnormal vertical placement
Exp Paradigm: Vertical pole test
 Vertical pole test
 Unreported
Motor coordination and balance1
Decreased
Description: Decreased motor learning demonstrating by No Change in latency to fall
Exp Paradigm: Male mice: Accelerating rotarod test
 Accelerating rotarod test
 Unreported
Head bobbing1
Increased
Description: Increased head pokes
Exp Paradigm: Novel environment hole-board test; Novel object test
 Hole-board test
 Unreported
Social interaction1
Decreased
Description: Decreased social interactions with tendency to participate in non-social self focused behaviors
Exp Paradigm: Dyadic test for social behavior
 Reciprocal social interaction test
 3-6 months
Social interaction1
Abnormal
Description: Abnormal social behavior demonstrated by decreased social affiliation however showed No Change in social preference
Exp Paradigm: Sociability test: Interaction with social or non-social stimulus, or social-social stimulus
 Three-chamber social approach test: sociability
 3-6 months
Ultrasonic vocalization1
Abnormal
Description: Abnormal ultrasonic vocalization: Increased number of calls, decreased call pattern complexity, No Change in call frequency across duration
Exp Paradigm: Male mice:
 
 3-4 months
Ultrasonic vocalization1
Abnormal
Description: Abnormal ultrasonic vocalization: Decreased number of calls, decreased call pattern complexity, increased high frequency calls for shorter durations
Exp Paradigm: Female mice:
 
 3-4 months
Size/growth1
Increased
Description: Increased body weight
Exp Paradigm: General observations
 General observations
 8-12 months
Gene expression1
Abnormal
Description: Abnormal Shank3 species indicated by two smaller products (330 bp and 260 bp)
Exp Paradigm: Shank3 Mrna Species
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased expression of full-length Shank3 protein
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
General characteristics1
 No Change
 General observations
 Unreported
Size/growth1
 No Change
 General observations
 3-4 months
Anxiety1
 No Change
 Light-dark exploration test; Elevated zero maze test
 Unreported
Response to novelty1
 No Change
 Open field test; Zero maze test
 Unreported
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Unreported
Olfaction1
 No Change
 
 Unreported
 Not Reported: Circadian sleep/wake cycle, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure

SHANK3_3_CN_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: NR1
Decreased
Description: Decreased levels of NMDAR subunit NR1 levels in cortex
Exp Paradigm: Immunoblot analysis from cortical lysates
 Western blot
 2 months
Synaptic transmission1
Decreased
Description: Decreased ratio of NMDA/AMPA-dependent evoked responses in cortex
Exp Paradigm: Whole cell recordings
 Whole-cell patch clamp
 Unreported
Protein ubiquitination1
Increased
Description: Increased polyubiquitination of Shank3 in cortex
Exp Paradigm: In Vivo Polyubiquitination
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased Shank3 protein levels in cortical lysates
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 8 weeks
Signaling2
Decreased
Description: Actin signaling is significantly downregulated in the prefrontal cortex of Shank3 het mice (ankyrin repeats deleted) determined by significant changes in expression profile from the cortical protein synaptic density (PSD) fractions , in two dimensional fluorescence difference gel electrophoresis. Significant reduction in p-cofilin (inactive cofilin) and LIMK1 were observed.
Exp Paradigm: Males only
 Two-dimensional flourescence difference gel electrophoresis (2-DIGE): actin levels in protein synaptic density (PSD) fraction
 6-8 weeks
General characteristics1
 No Change
 General observations
 Unreported
Size/growth1
 No Change
 General observations
 Unreported
Neuroreceptor levels: glutamate receptors: NR1
 No Change
 Western blot
 2 months
 Not Reported: Circadian sleep/wake cycle, Circadian sleep/wake cycle, Communications, Communications, Developmental profile, Emotion, Emotion, Homeostasis, Homeostasis, Immune response, Immune response, Learning & memory, Learning & memory, Maternal behavior, Maternal behavior, Molecular profile, Motor phenotype, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Neurophysiology, Repetitive behavior, Repetitive behavior, Seizure, Seizure, Sensory, Sensory, Social behavior

SHANK3_7_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Protein expression level evidence1
Increased
Description: Increased synaptic content of ionotropic glutamate receptor
Exp Paradigm: Ionotropic Glutamate Receptor Content
 
 Unreported
Protein expression level evidence1
Increased
Description: Increased Shank2 protein levels in whole brain PSD's
Exp Paradigm: Shank2 Protein Levels
 Western blot
 Unreported
Gene expression1
 No Change
 
 Unreported
Dendritic spine density and architecture1
 No Change
 Golgi-Cox staining
 Unreported
Synaptic morphology1
 No Change
 Electron microscopy
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_8_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3 mutant mice have reduced time to fall of the rotarod than wild type control animals.
Exp Paradigm: Males and females
 Accelerating rotarod test
 2-6 months
Synaptic neuroreceptors1
Increased
Description: Shank3 mutant mice have increased levels of mGluR5 in the synaptosomal and postsynaptic density fraction in the hippcampal lysates.
 Western blot: hippocampal lysate
 5-6 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: The frequencey of mEPSCs in hippocampal synapses in the Shank3 mutant mice was signficantly reduced, indicatinga possible decrease in the number of CA3-CA1 synapses
Exp Paradigm: Males only
 Whole-cell patch clamp
 P13-17
Synaptic plasticity: hippocampal LTP1
Decreased
Description: LTP was significantly impaired in the CA1 region of Shank3 mutants compared to wild type controls
Exp Paradigm: Males only
 Field potential recordings
 3-4 months
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Synaptic transmission dependent on the NMDAR/AMPAR ratio is reduced in Shank3 mutants. It is determined using amplitude/frequency of miniature EPScs that NMDAR mediated currents are reduced
Exp Paradigm: Males only
 Whole-cell patch clamp
 3-4 months
Synaptic transmission1
Decreased
Description: The input/output relationship of stimulus intensity to slope of fEPSP is decreased in Shank3 mutant mice, which may indicate a reduction in the number of functional CA3-CA1 synapses
Exp Paradigm: Males only
 Field potential recordings
 P13-17
Repetitive digging1
Decreased
Description: Shank3 mutant mice have a significantly reduced number of marbles buried in the marble burying test, compared to wild type controls
Exp Paradigm: Males and females
 Marble-burying test
 2-6 months
Self grooming: perseveration1
Increased
Description: Older Shank3 mutant mice have increased levels of grooming in the number of bouts and time spent, in a novel environment (new cage)
Exp Paradigm: Males and females
 Grooming behavior assessments
 10-13 months
Self grooming: perseveration3
Increased
Description: Excessive self-grooming in Shank3 KO but not Shank3 HT mice
Exp Paradigm: To monitor spontaneous self-grooming, mice were placed in a clean cage (identical to the home cage), with minimal bedding to discourage digging, which was then placed in a sound-proof box for video monitoring; Animals were habituated in the new cage for 10 minutes before self-grooming was monitored during another 10 minutes; Cumulative grooming time was reported for this second 10 minute period;
 Grooming behavior assessments
 Adult
Pain or nociception1
Increased
Description: Shank3 mutant mice show increased pain perception as the latency to lick their paw after a foot shock has been delivered is lower in these mice compared to wild type controls
Exp Paradigm: Males and females
 Hot plate test
 2-6 months
Inanimate object preference1
Decreased
Description: Shank3 mutant mice have a high propensity to avoid all new objects.
Exp Paradigm: Males and females
 Three-chamber social approach test
 2-6 months
Social approach2
Decreased
Description: Shank3 mutant mice have reduced preference for the stimulus mouse compared to wild type controls.
Exp Paradigm: Males only
 Three-chamber social approach test
 6-8 weeks
Social memory1
Decreased
Description: Shank3 mutant mice have reduced memory of a familiar stimulus mouse as they spend a similar amount of time interacting with the familiar and novel stimulus mice in the three chamber social approach test
Exp Paradigm: Males and females
 Three-chamber social approach test: interaction with juvenile target mice
 2-6 months
Nest building behavior1
Decreased
Description: Shank3 mutant mice show significantly reduced nest building behavior, showing no change in their nestlets, whereas wild type controls readily made nests from the material.
Exp Paradigm: Males and females
 Nest building assay
 2-6 months
Social approach3
Decreased
Description: Social investigation reduced in Shank3 KO but not Shank3 HT mice
Exp Paradigm: Mice were tested for social motivation and social novelty in a three-chamber arena over three phases; In Phase 1, identical inanimate objects (inverted ceramic cups with blue stripe) were placed in both side chambers; In phase 2, social interaction with a novel intruder is measured relative to a previously encountered object from phase 1; Phase 3 tests for social novelty with a second intruder;
 Three-chamber social approach test
 Adult
Exploratory activity3
Decreased
Description: Increased avoidance behavior or decreased exploratory behavior present in both Shank3 KO and HT mice
Exp Paradigm: Decreased marble-burying in both Shank3 KO and HT mice
 Marble-burying test
 Adult
Anxiety1
Increased
Description: Shank3 mutant mice show increased anxiety-like behavior in the light/dark box test as they have a very high latency to explore the dark box and spend very little tim in the dark box. Authors have noted that this may be attributable to increase in avoidance behavior, rather in increase in anxiety.
Exp Paradigm: Males and females
 Light-dark exploration test
 2-6 months
Response to novelty1
Decreased
Description: Shank3 mutants show reduced response to novelty, unlike wild type controls, as they have reduced locomotor activity in the novel environment of the open field test
Exp Paradigm: Males and females
 Open field test
 2-6 months
Spatial learning1
Decreased
Description: Shank3 mutant mice show reduced spatial learning measured by latency to reach the hidden platform, in the Morris water maze test. They take longer times to reach the platform compared to wild type controls
Exp Paradigm: Males and females
 Morris water maze test: latency and distance travelled in the hidden platform trials
 2-6 months
Spatial reference memory1
Decreased
Description: Shank3 mutant mice show significantly reduced memory of the position of the platform, despite spending increased amount of time in the correct quadrant compared to other quadrants. Number of crossings at the are significantly lower in shank3 mutants compared to wild type controls in both the probe trial and the probe trial of the reversal phase of Morris water maze
Exp Paradigm: Males and females
 Morris water maze test: probe trial and reversal phase probe trial
 2-6 months
Protein expression level evidence3
Increased
Description: Inreased CLK2 protein in knockout mice neurons;
Exp Paradigm: Primary cortical neurons were stimulated with BDNF (to elicit synaptic-plasticity dependent changes) on the 16th day in vitro and harvested in RIPA buffer for SDS-PAGE and Western blotting;
 Western blot;
 E16
Targeted protein expression2
Decreased
Description: Shank3 full length isoforms show a reduction of 85% in the synaptosomal and total fractions of frontal cortical lysates from homozygous knockout mice, compared to wild type
 Western blot: frontal cortex lysate
 
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
 No change
 Monitoring ultrasonic vocalizations
 10-13 months
Anxiety1
 No change
 Open field test: time spent in the center vs the periphery; Elevated plus maze test: time spent in the open arms
 2-6 months
Anxiety3
 No Change
 Elevated zero maze test
 Adult
Cognitive flexibility1
 No change
 Morris water maze test: reversal training phase
 2-6 months
General locomotor activity3
 No Change
 Open field test; Accelerating rotarod test;
 Adult
Dendritic spine density and architecture1
 No change
 Golgi-Cox staining; Sholl analysis
 P13-17, 6-8 months
Dendritic spine density and architecture: dendritic tree complexity1
 No change
 Golgi-Cox staining; Sholl analysis
 P13-17, 6-8 months
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: hippocampal lysate
 5-6 months
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: hippocampal lysate
 5-6 months
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp
 P13-17
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell patch clamp
 P13-17
Synaptic plasticity: hippocampal LTD1
 No change
 Field potential recordings
 6-8 weeks, 3-4 weeks
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 2-4.5 months
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 2-6 months
Sensorimotor gating1
 No change
 Prepulse inhibition
 2-6 months
Social approach1
 No change
 Three-chamber social approach test
 2-6 months
Social interaction1
 No change
 Reciprocal social interaction test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Circadian sleep/wake cycle, Communications, Communications, Developmental profile, Developmental profile, Emotion, Homeostasis, Homeostasis, Immune response, Immune response, Learning & memory, Learning & memory, Maternal behavior, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Neurophysiology, Repetitive behavior, Seizure, Seizure, Sensory, Sensory

SHANK3_9_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: NR1
Decreased
Description: Levesl of NR1 and NR2A are significantly reduced in the synaptosomal fraction of the frontal cortex from Shank3 het mice
Exp Paradigm: Males only
 Western blot:synaptosomal fraction of frontal cortex
 6-8 weeks
Dendritic spine density and architecture2
Decreased
Description: There is a reduction in spine density from Purkinje cell dendrites in Shank3 het mice, measured as number of spines per 10 micro meter on distal dendrites
Exp Paradigm: Males only
 Golgi-Cox staining; Sholl analysis: Purkinje cells
 2-4 months
Dendritic spine density and architecture: dendritic tree complexity2
Increased
Description: The distal dendrites of Purkinje cells have higher complexity compared to controls in Shank3 het mice
Exp Paradigm: Males only
 Golgi-Cox staining; Sholl analysis: Purkinje cells
 2-4 months
Synaptic transmission: excitatory1
Decreased
Description: NMDAR dependent EPSC was also reduced in the CA1 pyramidal neurons of the hippocampus in Shank3 het mice
Exp Paradigm: Males only
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 6-8 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR to AMPAR -EPSC ratio is significantly reduced in layer V pyramidal neurons of Shank3 het mice compared to wild type controls
Exp Paradigm: Males only
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
Decreased
Description: NMDAR dependent excitatory synaptic transmission in layer V pyramidal neurons is significantly reduced in the prefrontal cortex (PFC) of Shank3 het mice, compared to wild type.
Exp Paradigm: Males only
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Self grooming: perseveration1
Increased
Description: Shank3 het mice have increased time spent in self grooming compared to wild type controls
Exp Paradigm: Males only
 Grooming behavior assessments
 6-8 weeks
Social approach1
Decreased
Description: Shank3 het mice have significantly reduced preference to social stimulus compared to wild type controls
Exp Paradigm: Males only
 Three-chamber social approach test
 6-8 weeks
Eye blink conditioning2
Decreased
Description: Shank3 hets have significantly reduced learning of the conditioned response in eyeblink conditioning, compared to controls. The response amplitude of the eye-blink is also reduced
Exp Paradigm: Males only
 Eyeblink conditioning: probability of generating a response and response amplitude
 2-4 months
Eye blink conditioning2
Decreased
Description: Shank3 hets have a reduced reponse amplitude as well in the conditioned response, the authors state that this magnitude reflects the neural representation of the learned response
 Eyeblink conditioning: probability of generating a response
 
Cytoskeletal organization1
Decreased
Description: Similar to the decrease in F-actin in the PFC there is a reduction or loss of F actin in the hippocampus seen using phalloidin immunostaining
Exp Paradigm: Males only
 Immunostaining: hippocampal slices with phalloidin
 6-8 weeks
Enzyme activity1
Decreased
Description: There is decrease in the activity of Rac1/PAK1 signaling pathway enzymes including beta-PIX
Exp Paradigm: Males only
 Western blot
 6-8 weeks
Protein phosphorylation1
Decreased
Description: There is a significant reduction in protein phosphrylation levels, specifically for proteins involved in the Rac1 signaling pathway, including PAk1/2/3, LIMK and Cofilin.
Exp Paradigm: Males only
 Western blot: total lysate from PFC
 6-8 weeks
Cytoskeletal organization1
Decreased
Description: Decrease in the inactive form of cofilin leads to decreased levels or loss of F actin determined by levels of F-actin in the synapse, even when total levels of actin in the synaptic cytosol were similar between Shank3 hets and wild type controls (PFC lysate). This was confirmed using phalloidin immunostaining in PFC slices
Exp Paradigm: Males only
 Western blot: actin and F-actin levels; Immunostaining: phalloidin in PFC slices
 6-8 weeks
Enzyme activity1
Increased
Description: The activity of cofilin is increased following the reduction in phosphorylated (inactive) levels of cofilin as the Rac1 signaling pathway is reduced
Exp Paradigm: Males only
 Western blot
 6-8 weeks
Protein localization: synapse1
Decreased
Description: Based on comaprison between synaptosomal and total lysate fractions from the frontal cortex, there is reduced targeting of NR1 and NR2A NMDAR receptor subunits to the synapses in Shank3 het mice frontal cortices
Exp Paradigm: Males only
 Western blot:synaptosomal fraction and total lysate of frontal cortex
 6-8 weeks
Signaling1
Decreased
Description: The Rac1 signaling pathway is significantly downregulated in the prefrontal cortex of Shank3 het mice determined by the reduced levels of activated (phosphorylated) downstream effectors and increased levels of inactivated (phosphorylated) target protein cofilin.
Exp Paradigm: Males only
 Western blot: total lysate from PFC, levels of p-LIMK1, PAK1/2/3 and p-cofilin
 6-8 weeks
Anxiety1
 No change
 Open field test: time spent in the center vs the periphery
 6-8 weeks
Eye blink conditioning: extinction and reactivation2
 No change
 Eyeblink conditioning: response amplitude
 2-4 months
Spatial learning2
 No change
 Water Y-maze
 2-4 months
Cytoskeletal organization1
 No change
 Immunostaining: phalloidin in PFC slices
 6-8 weeks
Cytoskeletal organization1
 No change
 Immunostaining: striatal slices with phalloidin
 6-8 weeks
Gait2
 No change
 Running stride analysis
 2-4 months
General locomotor activity1
 No change
 Open field test
 6-8 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6-8 weeks
Cerebellar morphology: granule cell layer thickness2
 No change
 Histology
 2-4 months
Cerebellar morphology: molecular layer thickness2
 No change
 Histology
 2-4 months
Dendritic spine density and architecture1
 No change
 Golgi-Cox staining; Sholl analysis
 6-8 weeks
Neuronal number: Purkinje cells2
 No change
 Histology
 2-4 months
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot:synaptosomal fraction and total lysate of frontal cortex
 6-8 weeks
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot:synaptosomal fraction of frontal cortex
 6-8 weeks
Synapse density1
 No change
 Immunostaining: PSD95
 6-8 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp: medium spiny neurons of dorsal striatum
 6-8 weeks
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 6-8 weeks
Social approach1
 No change
 Three-chamber social approach test
 6-8 weeks
Social memory1
 No change
 Three-chamber social approach test
 6-8 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_10_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3G homozygous mice show reduced motor coordination and latency to fall off the accelerating rotarod
 Accelerating rotarod test
 2-6 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: The frequencey of mEPSCs in hippocampal synapses in the Shank3 mutant mice was signficantly reduced, indicatinga possible decrease in the number ofCA1 pyramidal neurons in the presence of tetradotoxin
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: hippocampal LTD1
Decreased
Description: The mGluR5-LTD is reduced in magnitude in Shank3G homozygous mice in the hippocampus
 Field potential recordings: CA1 region
 
Synaptic transmission1
Decreased
Description: The I/O curve shows a reduced slope of fEPSP in the CA1 region
 Field potential recordings: CA1 region
 
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: The ratio of NMDAR to AMPAR mediated EPSCs is reduced in Shank3G homozygous mice, authors indicated a reduction in NMDA mediated component of EPSC
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: post-tetanic potentiation (PTP)1
Decreased
Description: There is a decrease in the magnitude to post-tetanic potentiation in the first five minutes following the conditioning stimulus in the hippocampal slices from Shank3G homozygous mice
 Field potential recordings: CA1 region
 
Repetitive digging1
Decreased
Description: Shank3G homozygous mice show reduced marble-burying and the authors attribute this to increased novelty avoidance phenotype
 Marble-burying test
 2-6 months
Nest building behavior1
Decreased
Description: Shank3G homozygous mice show reduced nest building from nesting material and the authors characterize this as an increase in avoidance phenotype or response to novelty
 Nest building assay
 2-6 months
Response to novelty1
Decreased
Description: Shank3G mice show reduced response, determined by locomotor activity, compared to littermate wildtype controls in several tests when first introduced in the new environment of testing, like open field, elevated plus maze and light-dark exploration test
 Light-dark exploration test; Elevated plus maze test; Open field test
 5-6 months
Spatial learning1
Decreased
Description: Shank3G homozygous mice have reduced spatial learning in the morris water maze hidden platform task determined by distance travelled
 Morris water maze test
 2-6 months
Targeted protein expression1
Decreased
Description: There is loss of the wild type Shank3 protein in the homozygous Shank3G mice
 Western blot
 5-6 months
Protein phosphorylation1
Decreased
Description: Glun2B has decreased phosporylation at Ty2 1472 in the hippocampus
 Western blot: hippocampal synaptosomes
 5-6 months
Size/growth1
 No change
 
 
Anxiety1
 No change
 Light-dark exploration test; Elevated plus maze test; Open field test
 5-6 months
Thigmotaxis1
 No change
 Morris water maze test: visible platform test, hidden platform test and probe trial
 2-6 months
Spatial reference memory1
 No change
 Morris water maze test
 2-6 months
Protein phosphorylation1
 No change
 
 5-6 months
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Synaptic neuroreceptors1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Decay kinetics of evoked post synaptic currents1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: hippocampal LTP1
 No change
 Field potential recordings: CA1 region
 
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 2-6 months
Vision1
 No change
 Morris water maze test: visible platform test
 2-6 months
Social approach1
 No change
 Three-chamber social approach test
 2-6 months
Social memory1
 No change
 Three-chamber social approach test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Maternal behavior, Seizure

SHANK3_11_KI_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: hippocampal LTD1
Decreased
Description: The mGluR5-LTD is reduced in magnitude in Shank3G het mice in the hippocampus
 Field potential recordings
 
Synaptic transmission1
Decreased
Description: The I/O curve shows a reduced slope of fEPSP in the CA1 region
 Field potential recordings
 
Nest building behavior1
Decreased
Description: Shank3G het mice show reduced nest building from nesting material and the authors characterize this as an increase in avoidance phenotype or response to novelty
 Nest building assay
 2-6 months
Targeted protein expression1
Decreased
Description: There is 50% loss of the wild type Shank3 protein in the homozygous Shank3G het mice
 Western blot
 5-6 months
Size/growth1
 No change
 
 
Anxiety1
 No change
 Light-dark exploration test; Elevated plus maze test; Open field test
 5-6 months
Response to novelty1
 No change
 Light-dark exploration test; Elevated plus maze test; Open field test
 5-6 months
Thigmotaxis1
 No change
 Morris water maze test: visible platform test, hidden platform test and probe trial
 2-6 months
Spatial learning1
 No change
 Morris water maze test
 2-6 months
Spatial reference memory1
 No change
 Morris water maze test
 2-6 months
Protein phosphorylation1
 No change
 Western blot
 5-6 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 2-6 months
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Synaptic neuroreceptors1
 No change
 Western blot: hippocampal synaptosomes
 5-6 months
Decay kinetics of evoked post synaptic currents1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Presynaptic function: presynaptic fiber volley1
 No change
 Field potential recordings
 
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: hippocampal LTP1
 No change
 Field potential recordings
 
Repetitive digging1
 No change
 Marble-burying test
 2-6 months
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 2-6 months
Vision1
 No change
 Morris water maze test: visible platform test
 2-6 months
Social approach1
 No change
 Three-chamber social approach test
 2-6 months
Social memory1
 No change
 Three-chamber social approach test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Maternal behavior, Seizure

SHANK3_13_cKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: hippocampal LTP1
Decreased
Description: The magnitude of LTP in the CA1 region of Shank3 e4-9 HM mutants is significantly reduce compared to WT
Exp Paradigm: Males only
 Field potential recordings
 3-4 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR/AMPAR mediated synaptic transmission is reduced in the medium spiny neurons of the striatum in Shank3 e4-9 HM mutants
Exp Paradigm: Males only
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Self grooming: perseveration1
Increased
Description: Shank3 e4-9 HM mutants spend significantly increased time grooming compared to WT controls, authors note that the number of bouts was not different but the time spent in each bout was more
 Grooming behavior assessments: number of bouts and time spent in each bout of grooming
 3-5 months
Nest building behavior1
N o change
Description: Shank3 e4-9 HM mutants perform similarly to WT controls in nest building test and authors denote this as a function of normal levels of anxiety
 Nest building assay
 3-5 months
Social interaction1
Decreased
Description: Shank3 e4-9 HM mutants show reduced amount of time and number of instances of interaction in the reciprocal social interaction test requiring direct interaction with stimulus adult mouse
 Reciprocal social interaction test
 3-5 months
Ultrasonic vocalization: Isolation induced1
Increased
Description: Shank3 e4-9 HM mutants make significantly more calls than WT controls (the mother is Shank3 e4-9 het) at P4 and P6
 Monitoring ultrasonic vocalizations
 P4, P6
Thigmotaxis1
Increased
Description: Shank 3 e4-9 HM mutants show a significantly higher tendency for swimming close ot the walls in the Morris water maze test compared to hets or WT controls
 Morris water maze test
 3-5 months
Spatial reference memory1
Decreased
Description: Shank3 e4-9 HM mutants show no preference to a familiar object moved to a new location, unlike WT controls
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Object recognition memory1
Decreased
Description: Shank3 e4-9 HM mutants mice show no preference to a novel versus a familiar object
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Targeted protein expression1
Decreased
Description: Shank3 e4-9 HM mutants show a complete loss of the highest mol wt. band of Shank3 protein in the striatal lysate, detected by both C and N terminal antibodies, loss of C-3, C7 and N-3 bands are also noted, HM mutants showing a loss of several isoforms of Shank3
 Western blot: whole striatal lysate and striatal synaptosomal fraction
 3-6 months
Protein localization: synapse1
Decreased
Description: Shank3 e4-9 HM mutants have decreased levels of GluA2, GluA3, Homer 1b/c and PSD95 in the synaptosomal fraction from the striatum
 Western blot:striatal synaptosomal fraction
 3-6 months
Anxiety1
 No change
 Open field test; Light-dark exploration test; Elevated plus maze test; Marble-burying test
 3-5 months
Cognitive flexibility1
 No change
 Morris water maze test
 
Cued or contextual fear conditioning1
 No change
 Fear conditioning test
 
Spatial learning1
 No change
 Morris water maze test
 3-5 months
Spatial reference memory1
 No change
 Morris water maze test
 3-5 months
Protein localization: synapse1
 No change
 Western blot:striatal synaptosomal fraction
 3-6 months
General locomotor activity1
 No change
 Open field test
 
Motor coordination and balance1
 No change
 Accelerating rotarod test
 
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Presynaptic function: paired-pulse facilitation1
 No change
 Paired-pulse facilitation
 P14-P17
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp: hippocampus
 P14-P17
Synaptic plasticity: hippocampal LTD1
 No change
 Field potential recordings
 3-4 weeks
Synaptic transmission: excitatory1
 No change
 Field potential recordings
 3-4 weeks
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 3-5 months
Sensorimotor gating1
 No change
 Prepulse inhibition
 3-5 months
Vision1
 No change
 Morris water maze test
 3-5 months
Social interaction1
 No change
 Interaction with caged adult
 3-5 months
Social interaction: with juveniles1
 No change
 Reciprocal social interaction test
 3-5 months
Social memory1
 No change
 Reciprocal social interaction test: interaction with familiar juvenile mouse
 3-5 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

SHANK3_14_cKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR/AMPAR mediated synaptic transmission is reduced in the medium spiny neurons of the striatum in Shank3 e4-9 het mutants
Exp Paradigm: Males only
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Self grooming: perseveration1
Increased
Description: Shank3 e4-9 het mutants spend significantly increased time grooming compared to WT controls, authors note that the number of bouts was not different but the time spent in each bout was more
 Grooming behavior assessments: number of bouts and time spent in each bout of grooming
 3-5 months
Nest building behavior1
N o change
Description: Shank3 e4-9 het mutants show normal nest building tendency similar to WT, authors note this indicates normal levels of anxiety as well
 Nest building assay
 3-5 months
Ultrasonic vocalization: Isolation induced1
Increased
Description: Shank3 e4-9 Het mutants make significantly increased number of calls compared to WT controls at P4 and P12
 Monitoring ultrasonic vocalizations
 P4, P12
Object recognition memory1
Decreased
Description: Shank3 e4-9 Het mutants have no preference for novel object that replaces a familiar object
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Spatial reference memory1
Decreased
Description: Shank3 e4-9 Het mutants have no preference for a familiar object moved to a new location, unlike WT controls indicating reduced reference memory in the Object-place recognition test
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Targeted protein expression1
Decreased
Description: Shank3 e4-9 Het mutants have reduced levels of highest molecular weight bands of Shank 3 protein as expected in heterozygotes
 Western blot: whole striatal lysate and striatal synaptosomal fraction
 3-6 months
Anxiety1
 No change
 Open field test; Light-dark exploration test; Elevated plus maze test; Marble-burying test
 3-5 months
Thigmotaxis1
 No change
 Morris water maze test
 3-5 months
Cognitive flexibility1
 No change
 Morris water maze test
 3-5 months
Cued or contextual fear conditioning1
 No change
 Fear conditioning test
 
Spatial learning1
 No change
 Morris water maze test
 3-5 months
Spatial reference memory1
 No change
 Morris water maze test
 3-5 months
Protein localization: synapse1
 No change
 Western blot:striatal synaptosomal fraction
 3-6 months
General locomotor activity1
 No change
 Open field test
 3-5 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 3-5 months
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Presynaptic function: paired-pulse facilitation1
 No change
 Paired-pulse facilitation
 3-4 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp: hippocampus
 P14-P17
Synaptic plasticity: hippocampal LTD1
 No change
 Field potential recordings
 3-4 weeks
Synaptic plasticity: hippocampal LTP1
 No change
 Field potential recordings
 3-4 weeks
Synaptic transmission: excitatory1
 No change
 Field potential recordings
 3-4 weeks
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 3-5 months
Sensorimotor gating1
 No change
 Prepulse inhibition
 3-5 months
Vision1
 No change
 Morris water maze test
 3-5 months
Social interaction1
 No change
 Reciprocal social interaction test; Interaction with caged adult
 3-5 months
Social interaction: with juveniles1
 No change
 Reciprocal social interaction test
 3-5 months
Social memory1
 No change
 Reciprocal social interaction test
 3-5 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

SHANK3_15_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Shank3 InsG HM mice have reduced general locomotor activity in the open field compared to WT
 Open field test
 Adult
Motor coordination and balance1
Decreased
Description: Shank3 InsG HM mice have shorter latencies to fall off in the accelrating rotarod test compared to WT
 Accelerating rotarod test
 Adult
Dendritic spine density and architecture1
Decreased
Description: Shank3 InsG HM mutants had reduced dendritic spine density in layer 2/3 pyramidal neurons in the 'frontal association area', compared to WT
 Golgi-Cox staining: layer 2/3 pyramidal neurons; Histology
 2 months
Neuroreceptor levels: glutamate receptors: GluR1
Increased
Description: Shank3 InsG have increased levels of GluR1, corresponding to increased amplitude of mEPSCs, at P14, compared to WT
 Western blot: striatal synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
Decreased
Description: GluR2 and mGluR5 levels are decreased in Shank3 InsG HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NR1
Decreased
Description: NR1, NR2A and NR2B levels are decreased in Shank3 InsG HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 InsG HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 InsG HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Population spikes1
Decreased
Description: Shank3 InsG HM mutants had reduced evoked population spikes in the striatum compared to WT
 Field potential recordings: striatum
 Adult
Miniature post synaptic current amplitude: excitatory1
Increased
Description: At P14, Shank3 InsG HM mutants have increased amplitude of AMPA mediated mEPSCs in the dorsolateral striatal MSNs from WT
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Miniature post synaptic currents: excitatory1
Decreased
Description: NMDAR mediated mEPSCs are reduced in Shank3 InsG HM adults as well
 Whole-cell patch clamp: NMDAR mediated currents in striatal MSNs
 Adult
Population spikes1
Decreased
Description: Shank3 InsG HM mutants had reduced evoked population spikes in the striatum compared to WT
 Field potential recordings: striatum
 P14
Self grooming: perseveration1
Increased
Description: Shank3 InsG mutants spend almost twice as much time grooming compared to WT controls
 Grooming behavior assessments
 Adult
Sensorimotor gating1
Decreased
Description: Shank3 InsG have impaired prepulse inhibition compared to WT
 Prepulse inhibition
 Adult
Acoustic startle reflex1
Decreased
Description: Shank3 InsG have significantly impaired acoustic startle reflex and authors note that this complicated interpretation of PPI data
 Acoustic startle reflex test
 Adult
Social approach1
Decreased
Description: Shank3 InsG HM mutants display no preference for a stimilus mouse over an object, unlike WT controls
 Three-chamber social approach test
 Adult
Social memory1
Decreased
Description: Shank3 InsG HM mutants display no preference for a stranger mouse over a familiar mouse unlike WT controls
 Three-chamber social approach test
 Adult
Social dominance1
Increased
Description: Shank3InsG HM mutants have a higher propensity of winning in a social confrontation in the tube test
 Tube test of social dominance
 Adult
Juvenile play1
Decreased
Description: Shank3 InsG HM mutants show reduction in juvenile play with reduced nose-anogenital sniffing and following behavior compared to WT
 Reciprocal social interaction test
 3 weeks
Exploratory activity1
Decreased
Description: Shank3 InsG HM mutants have decreased exploratory activity in an environment determined by the amount of distance traveled
 Open field test
 Adult
Anxiety1
Increased
Description: Shank3 InsG HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
 Open field test; Elevated zero maze test
 Adult
Protein expression level evidence1
Increased
Description: Shank2 protein levels are increased in the cortical tissue of Shank3 InsG HM mutants
 Western blot: cortical tissue
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 InsG have decreased Homer at P14 in the striatal synaptosomal preparations compared to WT
 Western blot: striatal synaptic membrane proteins
 P14
Protein localization: synapse1
Decreased
Description: Shank3 InsG mutants have decreased levels of Homer 1b-c and Syngap1, Sapap3 in the striatal synaptosomal plasma membrane prep
 Western blot: striatal synaptic membrane proteins
 Adult
Protein localization: synapse1
Increased
Description: Increased levels of Shank2 proteins are observed in Shank3 InsG HM mutants
 Western blot: cortical synaptic membrane protein receptors
 P14
Protein localization: synapse1
Decreased
Description: Shank3 InsG HM mice have decreased levels of Homer 1b-c, PSD 95 and 93 in the cortial synaptic membrane prep from adult mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Targeted protein expression1
Decreased
Description: Shank3 InsG HM mutation results in loss of WT Shank3 and even the expected 135 kDa band of the truncated protein is also not detected in western blots, Shank3 mRNA levels are also severely reduced indicating possible degradation via the nonsense mediated decay
 Western blot: striatal lysate; Quantitative PCR (qRT-PCR)
 2 months
Gene expression1
Increased
Description: Shank2 and Shank2 mRNAs are increased in the cortical tissue of Shank3 InsG HM mutants
 Quantitative PCR (qRT-PCR): cortical tissue
 2 months
Ultrasonic vocalization: Isolation induced1
 No change
 Monitoring ultrasonic vocalizations: number, duration, peak amplitude of calls
 P2-P12
Exploratory activity: Habituation1
 No change
 Open field test
 Adult
Spatial working memory1
 No change
 T-maze test
 Adult
Protein localization: synapse1
 No change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: cortical synaptic membrane protein (SPM) receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Presynaptic function1
 No change
 Field potential recordings: striatum, negative peak1 measurement
 P14, adult
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Seizure

SHANK3_16_KI_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Shank3 InsG HT mutants display decreased distance traveled in the open field compared to WT indicating reduced activity
 Open field test
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Shank3 InsG HT mutants have decreased frequency of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Exploratory activity1
Decreased
Description: Shank3 InsG HT mutants have significantly reduced distance traveled compared to WT in the open field test indicating decrease in exploratory activity
 Open field test
 Adult
Anxiety1
Increased
Description: Shank3 InsG HT mutants have increased anxiety-like behavior as they spend less time in the open arms compared to WT
 Elevated zero maze test
 Adult
Targeted protein expression1
Decreased
Description: There is 50% reduction in WT Shank3 protein in Shank3 InsG HT mice
 Western blot: striatal synaptic membrane proteins
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 InsG HT mutants have reduced Homer protein in the synaptosomal plasma membrane preparation from the striatum
 Western blot: striatal synaptic membrane proteins
 Adult
Targeted protein expression1
Decreased
Description: There is 50% reduction in WT Shank3 protein in Shank3 R-X HT mice
 Western blot: striatal synaptic membrane proteins
 2 months
Exploratory activity: Habituation1
 No change
 Open field test
 Adult
Motor coordination and balance1
 No change
 Accelerating rotarod test
 Adult
Dendritic spine density and architecture1
 No change
 Golgi-Cox staining: layer 2/3 pyramidal neurons; Histology
 2 months
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Population spikes1
 No change
 Field potential recordings: striatum
 Adult
Presynaptic function1
 No change
 Field potential recordings: striatum, negative peak1 measurement
 Adult
Allogrooming: perseveration1
 No change
 Grooming behavior assessments
 Adult
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 5 months
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 Adult
Sensorimotor gating1
 No change
 Prepulse inhibition
 Adult
Social approach1
 No change
 Three-chamber social approach test
 Adult
Social dominance1
 No change
 Tube test of social dominance
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure

SHANK3_17_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Shank3 InsG HM mice have reduced general locomotor activity in the open field compared to WT
 Open field test
 Adult
Motor coordination and balance1
Decreased
Description: Shank3 InsG HM mice have shorter latencies to fall off in the accelrating rotarod test compared to WT
 Accelerating rotarod test
 Adult
Dendritic spine density and architecture1
Decreased
Description: Shank3 R-X HM mutants had reduced dendritic spine density in layer 2/3 pyramidal neurons in the 'frontal association area', compared to WT
 Golgi-Cox staining: layer 2/3 pyramidal neurons; Histology
 2 months
Neuroreceptor levels: glutamate receptors: NR1
Decreased
Description: NR1, NR2A and NR2B levels are decreased in Shank3 R-X HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: GluR1
Decreased
Description: GluR2 and mGluR5 levels are decreased in Shank3 R-X HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NR1
Decreased
Description: There is decrease in the levels of NR1 and its partner Syngap1 in the cortical SPM prep from Shank3 R-X HM mutant mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 R-X HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 R-X HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Miniature EPSC frequency and amplitude are both reduced Shank3 R-X HM mutants (this mutation isreported in schizophrenia patients) in the pyramidal neurons of the prefrontal cortex
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Population spikes1
Decreased
Description: Shank3 R-X HM mutants have reduced evoked population spikes compared to WT in the striatum in adult mice, unlike at P14
 Field potential recordings: striatum
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Miniature EPSC frequency and amplitude are both reduced Shank3 R-X HM mutants (this mutation is reported in schizophrenia patients) in the pyramidal neurons of the prefrontal cortex
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
Increased
Description: Miniature EPSC amplitude is increased in Shank3 R-X HM mutants in the pyramidal neurons of the prefrontal cortex at P14
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Miniature post synaptic currents: excitatory1
Decreased
Description: NMDAR mediated mEPSCs are reduced in Shank3 InsG HM adults as well
 Whole-cell patch clamp: NMDAR mediated currents in striatal MSNs
 Adult
Sensorimotor gating1
Decreased
Description: Shank3 R-X have impaired prepulse inhibition compared to WT
 Prepulse inhibition
 Adult
Acoustic startle reflex1
Decreased
Description: Shank3 R-X have significantly impaired acoustic startle reflex and authors note that this complicated interpretation of PPI data
 Acoustic startle reflex test
 Adult
Social dominance1
Increased
Description: Shank3 R-X HM mutants have a higher propensity of winning in a social confrontation in the tube test
 Tube test of social dominance
 Adult
Social approach1
Decreased
Description: Shank3 R-X HM mutants display no preference for a stimulus mouse over an object, unlike WT controls
 Three-chamber social approach test
 Adult
Social memory1
Decreased
Description: Shank3 R-X HM mutants display no preference for a stranger mouse over a familiar mouse unlike WT controls
 Three-chamber social approach test
 Adult
Exploratory activity1
Decreased
Description: Shank3 R-X HM mutants have decreased exploratory activity in an environment determined by the amount of distance traveled
 Open field test
 Adult
Anxiety1
Increased
Description: Shank3 R-X HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
 Open field test; Elevated zero maze test
 Adult
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mice have decreased levels of Homer 1b-c, PSD 95 and 93 in the cortial synaptic membrane prep from adult mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mutants have slight but significant decrease in Homer protein in the cortical synaptic membrane preparation at P14
 Western blot: cortical synaptic membrane protein receptors
 P14
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mutants have decreased levels of Homer 1b-c and Syngap1, Sapap3 in the striatal synaptosomal plasma membrane prep
 Western blot: striatal synaptic membrane proteins
 Adult
Targeted protein expression1
Decreased
Description: Shank3 R-X HM mutation results in the production of the 122kDa truncated protein that is expected following the mutation, detected using a N term antibody, while the SHank3 mRNA is detected at a higher levels than in InsG mutants
 Western blot: striatal lysate; Quantitative PCR (qRT-PCR)
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM have decreased Homer protein at P14 in the striatal synaptosomal preparations compared to WT
 Western blot: striatal synaptic membrane proteins
 P14
Ultrasonic vocalization: Isolation induced1
 No change
 Monitoring ultrasonic vocalizations: number, duration, peak amplitude of calls
 P2-P12
Exploratory activity: Habituation1
 No change
 Open field test
 Adult
Spatial working memory1
 No change
 T-maze test
 Adult
Gene expression1
 No change
 Quantitative PCR (qRT-PCR): cortical tissue
 2 months
Protein expression level evidence1
 No change
 Western blot: cortical tissue
 2 months
Protein localization: synapse1
 No change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: striatal synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NR1
 No change
 Western blot: cortical synaptic membrane protein receptors
 P14
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Population spikes1
 No change
 Field potential recordings: striatum
 P14
Presynaptic function1
 No change
 Field potential recordings: straitum
 P14, adult
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 5 months
Juvenile play1
 No change
 Reciprocal social interaction test
 3 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure

SHANK3_18_KI_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic spine density and architecture1
Decreased
Description: SHank3 R-X HT mutants have reduced spine density in layer 2/3 pyramidal neurons
 Golgi-Cox staining: layer 2/3 pyramidal neurons; Histology
 2 months
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Shank3 R-X HT mutants have small but significant decrease in the amplitude of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Shank3 R-X HT mutants have significant reduction in the amplitude of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Allogrooming: perseveration1
Increased
Description: Shank3 R-X HT mutants show increased propensity of allogrooming cage mates than WT
 Grooming behavior assessments
 Adult
Social dominance1
Increased
Description: Shank3 R-X HT mutants show increased dominant behavior and propensity of winning in social confrontation in the tube test than WT
 Tube test of social dominance
 Adult
Social approach1
Decreased
Description: Shank3 R-X HT mutants show decreased sociability and preference for social target compared to an object in the three chamber test
 Three-chamber social approach test
 Adult
Anxiety1
Increased
Description: Shank3 R-X HT mutants have increased anxiety-like behavior in the OF
 Elevated zero maze test: time spent in open arms
 Adult
Protein localization: synapse1
Decreased
Description: Shank3 R-X HT mutants have reduced Homer protein in the synaptosomal plasma membrane preparation from the striatum
 Western blot: striatal synaptic membrane proteins
 Adult
Exploratory activity1
 No change
 Open field test: distance traveled
 Adult
Exploratory activity: Habituation1
 No change
 Open field test
 Adult
General locomotor activity1
 No change
 Open field test
 Adult
Motor coordination and balance1
 No change
 Accelerating rotarod test
 Adult
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Population spikes1
 No change
 Field potential recordings: striatum
 Adult
Presynaptic function1
 No change
 Field potential recordings: striatum, negative peak1 measurement
 Adult
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 Adult
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 Adult
Sensorimotor gating1
 No change
 Prepulse inhibition
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure

SHANK3_8_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Exploratory activity1
Decreased
Description: Increased avoidance behavior or decreased exploratory behavior present in both Shank3 KO and HT mice
Exp Paradigm: Decreased marble-burying in both Shank3 KO and HT mice
 Marble-burying test
 Adult
Anxiety1
 No Change
 Elevated zero maze test
 Adult
General locomotor activity1
 No Change
 Open field test; Accelerating rotarod test
 Adult
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure, Sensory

SHANK3_19_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: Ambulatory activity1
Decreased
Description: Shank3 null mice are hypoactive in their home cage
 Home cage behavior
 Adult
Self grooming: artificial stress evoked1
Increased
Description: Increased grooming is observed after splashing in Shank3 nulls (tested in Shank3 null mice that did not develop lesions)
Exp Paradigm: splashing test conducted in mice that did not show excessive self grooming behavior in home cage
 Grooming behavior assessments
 4-7 months
General locomotor activity1
Decreased
Description: Shank3 null mice display hypoactivity, with reduced rearing and locomotion in open field test as well
 Open field test
 Adult
Motor coordination and balance1
Decreased
Description: Shank3 null mice display a reduced latency to fall off steady state or accelerating rotarod
 Accelerating rotarod test
 >2 months
DTI: Fractional anisotropy or Relative anisotropy in brain regions1
Decreased
Description: Areas exhibiting reduced FA include genu of the corpus callosum, vingulum, anterior commissure, fimbria, optic tract, nigrostriatal bundles, cerebral peduncles, cerebellum and brainstem
 Diffusion Tensor imaging (DTI)
 2-2.5 months
Morphology and size of anterior commissure1
Decreased
Description: Anterior commissure is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology and size of stria terminalis1
Decreased
Description: Strial terminalis white matter tracts are smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology and size of the optic tract1
Decreased
Description: Optic tract is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology of the basal ganglia: Lentiform nucleus: Globus pallidus1
Increased
Description: Volume of the globus pallidus (grey matter) is increased in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Neuroreceptor levels: glutamate receptors: GluR1
Decreased
Description: GluN2A levels are reduced in the hippocampus of Shank3 null mice
 Western blot: hippocampus
 8 weeks
Olfactory bulb morphology1
Decreased
Description: Olfactory areas are smaller than controls in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Thalamic morphology1
Increased
Description: Volume of the thalamus is increased in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Dendritic spine density and architecture1
Decreased
Description: Striatal MSNs have reduced spine density in Shank3 null mice, combined with reduced frequency of SEPSCs, authors suggest a loss in excitatory synapses
 Golgi-Cox staining: striatal medium spiny neurons
 8 weeks
Hippocampal morphology1
Decreased
Description: Hippocampus is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology and size of fimbria1
Decreased
Description: Fimbria is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology and size of the corpus callosum1
Decreased
Description: Corpus callosum is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology of the amygdala1
Decreased
Description: The amygdala is smaller in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Morphology of the basal ganglia: Striatum: Caudoputamen1
Increased
Description: Volume of the striatal caudate putamen is increased in Shank3 null mice
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Neuroreceptor levels: glutamate receptors: mGluR1
Increased
Description: mGluR5 levels are increased in the striatum in Shank3 null mice including in the postsynaptic density
 Western blot: striatum; Immunostaining
 8 weeks
Post-synaptic density size1
Decreased
Description: Striatal MSNs have reduced PSD size (length and thickness) in Shank3 null mice
 Electron microscopy: striatal medium spiny neurons (MSNs)
 8 weeks
Event related oscillations (EROs) in electroencephalography (EEG): coherence1
Decreased
Description: A smaller task-induced increase in coherence is observed in the limbic network of Shank3 null mice
 In vivo local field potential (LFP) recordings: limbic network
 3-4 months
Spontaneous post synaptic event frequency: excitatory currents1
Decreased
Description: SEPSC frequency is reduced in the striatal MSNs of Shank3 null mice
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Action potential firing1
Increased
Description: Striatal MSNs have increased spikes in response to depolarizing steps of current in Shank3 null mice indicating a tendency for hyper-excitability
 Whole-cell patch clamp: striatal MSNs
 2-5 months
Event related oscillations (EROs) in electroencephalography (EEG)
Decreased
Description: Reduced oscillatory power is noted in the nucleus accumbens in the 7-11 Hz band of Shank3 null mice both before and after being exposed ot a social stimulus
 In vivo local field potential (LFP) recordings: after exposure to social stimulus
 3-4 months
Presynaptic function1
Decreased
Description: After a HFS probability of presynaptic release did not increase significantly in Shank3 null mice, unlike controls where HFS causes an increase in the probability of release
 High-frequency stimulation (HFS)
 2-5 months
Synaptic plasticity: striatal LTD1
Decreased
Description: Striatal LTD measured in the MSN synapses is reduced significantly in Shank3 null mice
 Whole-cell patch clamp: dorsostriatal medium spiny neurons
 2-5 months
Action potential firing1
Decreased
Description: Shank3 null mice also displayed lower unit firing rates in Nac both before and after introduction of the social stimulus
 In vivo local field potential (LFP) recordings: nucleus accumben (Nac)
 3-4 months
Self grooming: perseveration1
Increased
Description: Skin lesions were observed in greated than 50% Shank3 null mice caused by excessive self-grooming
 Grooming behavior assessments
 4-7 months
Acoustic startle reflex1
Decreased
Description: Shank3 null mice have reduced acoustic startle reflex
 Acoustic startle reflex test
 Adult
Self grooming: social context1
Increased
Description: During reciprocal social interaction test Shank3 null mice showed more self-grooming than controls
 Reciprocal social interaction test; Grooming behavior assessments
 >2 months
Social scent marking or recognition1
Decreased
Description: No preference towards own home nest versus a similar one is observed in Shank3 nulls, even if Shank3 null pups perform similar to controls when only one nest sample is provided
 Homing test
 P15
Social dominance1
Decreased
Description: Dominance was not maintained across days in triads containing 3 unfamiliar Shank3 null adults, unlike in wild type triads where dominance ranking was established in a day and maintained till day 6
 Dominance hierarchy formation
 >2 months
Ultrasonic vocalization: Isolation induced1
Decreased
Description: Shank3 null pups make fewer calls of decreased duration compared to control pups after being separated from mother
 Monitoring ultrasonic vocalizations
 P4
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
Decreased
Description: Adult male Shank3 null mice make fewer calls of shorter duration in response to female in estrus, compared to controls
 Monitoring ultrasonic vocalizations
 Adult
Developmental trajectory1
Decreased
Description: Shank3 null mice have some delays in achieving developmental milestones, like ear opening and paw positioning
 General observations
 P4
Anxiety1
Increased
Description: Shank3 null mice have increased latency to enter the lighted chamber than littermate and also try to escape from all new environments
 Light-dark exploration test
 Adult
Exploratory activity1
Decreased
Description: Shank3 null mice have a high tendency to escape from any new environment and do not show normal exploratory activity
 Home cage behavior; Novel cage test
 Adult
Cognitive flexibility1
Decreased
Description: Shank3 null mice have significant impairment in the reversal phase of Morris water maze test compared to controls
 Morris water maze test: reversal training phase
 Adult
Spatial reference memory1
Decreased
Description: Shank3 null mice have impaired memory of the target quadrant in the probe trial
 Morris water maze test: probe trial and reversal phase probe trial
 Adult
Reward reinforced choice behavior1
Decreased
Description: Shank3 null mice do not learn the task in which food pellet is 'earned' after lever-press in the 7 days of continuous reinforcement training, a striatal dependent task
 Operant conditioning paradigm: continuous reinforcement training
 Adult
Protein phosphorylation1
Increased
Description: Phosphorylated forms of Erk 1 and 2 (p-ERK 1/2)and S6K (p-S6K) are increased in Shank3 null mice
 Western blot: striatum
 8 weeks
Protein localization: synapse1
Decreased
Description: Homer2, Homer 1b/c are reduced in the striatal and hippocampal synapses while SAPAP and SAPAP3 are reduced in the synapses only in the striatal synapses of Shank3 null mice
 Western blot: striatum and hippocampus
 8 weeks
Mortality/lethality1
 No change
 General observations
 Adult
Size/growth1
 No change
 Body weight measurement
 P21, 3-6 months
Cued or contextual fear conditioning: Memory of context1
 No change
 Fear conditioning test
 Adult
Cued or contextual fear conditioning: Memory of cue1
 No change
 Fear conditioning test
 Adult
Olfactory learning and memory1
 No change
 Olfactory habituation-dishabituation test
 2 months
Spatial learning1
 No change
 Morris water maze test
 Adult
Gene expression1
 No change
 Quantitative PCR (qRT-PCR): striatum and hippocampus
 8 weeks
Grip strength1
 No change
 Grip strength test
 
Swimming ability1
 No change
 Morris water maze test: visible platform phase
 Adult
Dendritic spine density and architecture1
 No change
 Golgi-Cox staining: hippocampal neurons
 8 weeks
Morphology and size of fornix1
 No change
 Magnetic resonance histology (MRH); Voxel based morphometry
 2-2.5 months
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: striatum
 8 weeks
Post-synaptic density size1
 No change
 Electron microscopy: hippocampal neurons
 8 weeks
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Spontaneous post synaptic event amplitude: excitatory currents1
 No change
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Repetitive nose pokes1
 No change
 Hole-board test
 4-7 months
Seizures1
 No change
 Observation of seizures
 Adult
Sensorimotor gating1
 No change
 Prepulse inhibition
 Adult
Vision1
 No change
 Morris water maze test: visible platform phase
 Adult
Social approach1
 No change
 Three-chamber social approach test
 >2 months
Social interaction1
 No change
 Reciprocal social interaction test
 >2 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_19_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Ultrasonic vocalization: Isolation induced1
 No change
 Monitoring ultrasonic vocalizations
 P4
Anxiety1
 No change
 Light-dark exploration test
 Adult
Cognitive flexibility1
 No change
 Morris water maze test: probe trial and reversal phase probe trial
 Adult
Olfactory learning and memory1
 No change
 Olfactory habituation-dishabituation test
 Adult
Spatial learning1
 No change
 Morris water maze test
 Adult
Spatial reference memory1
 No change
 Morris water maze test: probe trial and reversal phase probe trial
 8 weeks
Protein localization: synapse1
 No change
 Western blot
 Adult
General locomotor activity1
 No change
 Open field test
 Adult
Grip strength1
 No change
 Grip strength test
 Adult
Neuroreceptor levels: glutamate receptors: GluR1
 No change
 Western blot: hippocampus
 8 weeks
Repetitive nose pokes1
 No change
 Hole-board test
 Adult
Sensorimotor gating1
 No change
 Prepulse inhibition
 Adult
Vision1
 No change
 Morris water maze test: visible platform phase
 Adult
Social approach1
 No change
 Three-chamber social approach test
 Adult
Social interaction1
 No change
 Reciprocal social interaction test
 Adult
Social memory1
 No change
 Three-chamber social approach test
 Adult
Social scent marking or recognition1
 No change
 Homing test
 Adult
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neurophysiology, Seizure

SHANK3_20_CKO_HM_NAc

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Action potential firing1
Decreased
Description: Striatal MSNs have significantly reduced spiking frequency in mutants with Shank3 knocked out in the Nac, compared to controls, indicating that the loss of Shank3 locally and specifically in the NAc causes the reduction in spiking, similar to what is observed in the complete KO
 In vivo local field potential (LFP) recordings: nucleus accumben (Nac)
 3-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

SHANK3_4_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Touch1
Increased
Description: Shank3 hets show an increased response to just air puff indicating aberrant sensitivity or hypersensitivity
 Response to air puff
 6-8 weeks
Sensorimotor gating: tactile cue1
Decreased
Description: Tactile prepulse inhibition responses are enhanced in Shank3 het mice, as opposed to control littermates that display reduced magnitude of acoustic startle response when they receive an air puff prepulse
 Prepulse inhibition: air puff stimulus
 6-8 weeks
Tactile discrimination and memory1
Decreased
Description: Shank3 hets have reduced discrimination and memory for objects differing in texture (rough or smooth) and do not preferentially interact with a novel textured-object over a familiar one
 Textured novel object recognition test (T-NORT)
 6-8 weeks
Object recognition memory: long-term recall1
Decreased
Description: Shank3 het mice have reduced preference for novel object when the retention period (or interval) is extended to 1 hr from 5 min, whereas WT mice still prefer the novel object
 Novel object recognition test
 6-8 weeks
Exploratory activity1
 No change
 Textured novel object recognition test (T-NORT)
 6-8 weeks
Object recognition memory1
 No change
 Novel object recognition test
 6-8 weeks
Acoustic startle reflex1
 No change
 Acoustic startle reflex test
 6-8 weeks
Sensorimotor gating1
 No change
 Prepulse inhibition
 6-8 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABI2 abl-interactor 2 10152 Q9NYB9 Y2H
Sakai Y , et al. 2011
ACTN1 actinin, alpha 1 87 P12814 Y2H; IP/WB; GST
Sakai Y , et al. 2011
ACTN2 actinin, alpha 2 88 P35609 Y2H
Sakai Y , et al. 2011
AGAP7 ArfGAP with GTPase domain, ankyrin repeat and PH domain 7 653268 Q5VUJ5 Y2H
Sakai Y , et al. 2011
ALDOA aldolase A, fructose-bisphosphate 226 P04075 Y2H
Sakai Y , et al. 2011
ANKRD35 ankyrin repeat domain 35 148741 Q8N283 Y2H
Sakai Y , et al. 2011
APP amyloid beta (A4) precursor protein 351 P05067 Y2H
Sakai Y , et al. 2011
ARPC2 actin related protein 2/3 complex, subunit 2, 34kDa 10109 O15144 Y2H
Sakai Y , et al. 2011
ARPC5L actin related protein 2/3 complex, subunit 5-like 81873 Q9BPX5 Y2H
Sakai Y , et al. 2011
ATN1 atrophin 1 1822 P54259 Y2H
Sakai Y , et al. 2011
C1QBP complement component 1, q subcomponent binding protein 708 Q07021 Y2H
Sakai Y , et al. 2011
C6orf154 chromosome 6 open reading frame 154 221424 Q5JTD7 Y2H
Sakai Y , et al. 2011
CA10 carbonic anhydrase X 56934 Q9NS85 Y2H
Sakai Y , et al. 2011
CALCOCO1 calcium binding and coiled-coil domain 1 57658 Q9P1Z2 Y2H
Sakai Y , et al. 2011
CAMK2B calcium/calmodulin-dependent protein kinase II beta 816 Q13554 Y2H
Sakai Y , et al. 2011
CCT3 chaperonin containing TCP1, subunit 3 (gamma) 7203 P49368 Y2H
Sakai Y , et al. 2011
CENPJ centromere protein J 55835 Q9HC77 Y2H
Sakai Y , et al. 2011
CEP72 centrosomal protein 72kDa 55722 Q9P209 Y2H
Sakai Y , et al. 2011
CLTA clathrin, light chain A 1211 P09496 Y2H
Sakai Y , et al. 2011
CLU clusterin 1191 P10909 Y2H
Sakai Y , et al. 2011
COPS6 COP9 constitutive photomorphogenic homolog subunit 6 (Arabidopsis) 10980 Q7L5N1 Y2H
Sakai Y , et al. 2011
COQ5 coenzyme Q5 homolog, methyltransferase (S. cerevisiae) 84274 Q5HYK3 Y2H
Sakai Y , et al. 2011
CRELD1 cysteine-rich with EGF-like domains 1 78987 Q96HD1 Y2H
Sakai Y , et al. 2011
CSNK1D casein kinase 1, delta 1453 P48730 Y2H
Sakai Y , et al. 2011
CTNND2 catenin (cadherin-associated protein), delta 2 1501 Q9UQB3 IP/WB
Quitsch A , et al. 2005
CYP51A1 cytochrome P450, family 51, subfamily A, polypeptide 1 1595 Q16850 Y2H
Sakai Y , et al. 2011
CYTIP cytohesin 1 interacting protein 9595 O60759 Y2H
Sakai Y , et al. 2011
DCTN2 dynactin 2 (p50) 10540 Q13561 Y2H
Sakai Y , et al. 2011
DDB1 damage-specific DNA binding protein 1, 127kDa 1642 Q16531 Y2H
Sakai Y , et al. 2011
DNAJA3 DnaJ (Hsp40) homolog, subfamily A, member 3 9093 Q96EY1 Y2H
Sakai Y , et al. 2011
DNM2 dynamin 2 1785 P50570 Y2H
Sakai Y , et al. 2011
EFEMP1 EGF containing fibulin-like extracellular matrix protein 1 2202 Q12805 Y2H
Sakai Y , et al. 2011
EFEMP2 EGF containing fibulin-like extracellular matrix protein 2 30008 O95967 Y2H
Sakai Y , et al. 2011
EID1 EP300 interacting inhibitor of differentiation 1 23741 Q9Y6B2 Y2H
Sakai Y , et al. 2011
ELAVL1 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R) 1994 Q15717 Y2H
Sakai Y , et al. 2011
ERI3 ERI1 exoribonuclease family member 3 79033 O43414 Y2H
Sakai Y , et al. 2011
FAM13A family with sequence similarity 13, member A 10144 O94988 Y2H
Sakai Y , et al. 2011
FAM92A1 family with sequence similarity 92, member A1 137392 A1XBS5 Y2H
Sakai Y , et al. 2011
FBXO7 F-box protein 7 25793 Q9Y3I1 Y2H
Sakai Y , et al. 2011
FKBP8 FK506 binding protein 8, 38kDa 23770 Q14318 Y2H
Sakai Y , et al. 2011
FLNA filamin A, alpha 2316 P21333 Y2H; IP/WB; GST
Sakai Y , et al. 2011
FRS3 fibroblast growth factor receptor substrate 3 10817 O43559 Y2H
Sakai Y , et al. 2011
FRYL FRY-like 285527 O94915 Y2H
Sakai Y , et al. 2011
GAPDH glyceraldehyde-3-phosphate dehydrogenase 2597 P04406 Y2H
Sakai Y , et al. 2011
GOT1 glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1) 2805 P17174 Y2H
Sakai Y , et al. 2011
GPR162 G protein-coupled receptor 162 27239 Q16538 Y2H
Sakai Y , et al. 2011
GPS1 G protein pathway suppressor 1 2873 Q13098 Y2H
Sakai Y , et al. 2011
GRN granulin 2896 P28799 Y2H
Sakai Y , et al. 2011
HAGH hydroxyacylglutathione hydrolase 3029 Q16775 Y2H
Sakai Y , et al. 2011
HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1 348980 O60741 IP/WB
Yi F , et al. 2016
HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2 610 Q9UL51 IP/WB
Yi F , et al. 2016
HCN3 hyperpolarization activated cyclic nucleotide gated potassium channel 3 57657 Q9P1Z3 IP/WB
Yi F , et al. 2016
HECW1 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 23072 Q76N89 Y2H
Sakai Y , et al. 2011
HGS hepatocyte growth factor-regulated tyrosine kinase substrate 9146 O14964 Y2H
Sakai Y , et al. 2011
HNRNPC heterogeneous nuclear ribonucleoprotein C (C1/C2) 3183 P07910 Y2H; GST
Sakai Y , et al. 2011
HNRNPK heterogeneous nuclear ribonucleoprotein K 3190 P61978 Y2H
Sakai Y , et al. 2011
ICA1 islet cell autoantigen 1, 69kDa 3382 Q05084 Y2H
Sakai Y , et al. 2011
IGSF9 immunoglobulin superfamily, member 9 57549 Q9P2J2 Y2H
Sakai Y , et al. 2011
ITGBL1 integrin, beta-like 1 (with EGF-like repeat domains) 9358 O95965 Y2H
Sakai Y , et al. 2011
ITSN1 intersectin 1 (SH3 domain protein) 6453 Q15811 Y2H
Sakai Y , et al. 2011
JAG2 jagged 2 3714 Q9Y219 Y2H
Sakai Y , et al. 2011
KHDRBS1 KH domain containing, RNA binding, signal transduction associated 1 10657 Q07666 Y2H
Sakai Y , et al. 2011
KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3 10656 O75525 Y2H; GST
Sakai Y , et al. 2011
KIAA0232 KIAA0232 9778 Q92628 Y2H
Sakai Y , et al. 2011
LINGO1 leucine rich repeat and Ig domain containing 1 84894 Q96FE5 Y2H
Sakai Y , et al. 2011
LOC727948 LOC727948similar to KIAA0454 protein 727948 N/A Y2H
Sakai Y , et al. 2011
LPHN1 latrophilin 1 22859 O94910 Y2H
Sakai Y , et al. 2011
LRRC7 leucine rich repeat containing 7 57554 Q96NW7 IP/WB
Quitsch A , et al. 2005
LTBP3 latent transforming growth factor beta binding protein 3 4054 Q9NS15 Y2H
Sakai Y , et al. 2011
LTBP4 latent transforming growth factor beta binding protein 4 8425 Q8N2S1 Y2H
Sakai Y , et al. 2011
MBIP MAP3K12 binding inhibitory protein 1 51562 Q9NS73 Y2H
Sakai Y , et al. 2011
MBOAT7 membrane bound O-acyltransferase domain containing 7 79143 Q96N66 Y2H
Sakai Y , et al. 2011
MCRS1 microspherule protein 1 10445 Q96EZ8 Y2H
Sakai Y , et al. 2011
MDH2 malate dehydrogenase 2, NAD (mitochondrial) 4191 P40926 Y2H
Sakai Y , et al. 2011
MEGF10 multiple EGF-like-domains 10 84466 Q96KG7 Y2H
Sakai Y , et al. 2011
MEGF11 multiple EGF-like-domains 11 84465 A6BM72 Y2H
Sakai Y , et al. 2011
MEGF6 multiple EGF-like-domains 6 1953 O75095 Y2H
Sakai Y , et al. 2011
MIPOL1 mirror-image polydactyly 1 145282 Q8TD10 Y2H
Sakai Y , et al. 2011
MT-CO2 Cytochrome c oxidase subunit 2 4513 P00403 Y2H
Sakai Y , et al. 2011
MT-ND6 mitochondrially encoded NADH dehydrogenase 6 4541 P03923 Y2H
Sakai Y , et al. 2011
MYO5B myosin VB 4645 Q9ULV0 Y2H
Sakai Y , et al. 2011
N4BP3 NEDD4 binding protein 3 23138 O15049 Y2H
Sakai Y , et al. 2011
NCKIPSD NCK interacting protein with SH3 domain 51517 Q9NZQ3 Y2H
Sakai Y , et al. 2011
NEFL neurofilament, light polypeptide 4747 P07196 Y2H
Sakai Y , et al. 2011
NELL2 NEL-like 2 (chicken) 4753 Q99435 Y2H; GST
Sakai Y , et al. 2011
NGRN neugrin, neurite outgrowth associated 51335 Q9NPE2 Y2H
Sakai Y , et al. 2011
NOTCH1 notch 1 4851 P46531 Y2H
Sakai Y , et al. 2011
NOTCH2 notch 2 4853 Q04721 Y2H
Sakai Y , et al. 2011
NOTCH2NL notch 2 N-terminal like 388677 Q7Z3S9 Y2H
Sakai Y , et al. 2011
NOTCH3 notch 3 4854 Q9UM47 Y2H
Sakai Y , et al. 2011
NR1D1 nuclear receptor subfamily 1, group D, member 1 9572 P20393 Y2H
Sakai Y , et al. 2011
NRBF2 nuclear receptor binding factor 2 29982 Q96F24 Y2H
Sakai Y , et al. 2011
PDHB pyruvate dehydrogenase (lipoamide) beta 5162 P11177 Y2H
Sakai Y , et al. 2011
PFKL phosphofructokinase, liver 5211 P17858 Y2H
Sakai Y , et al. 2011
PHF12 PHD finger protein 12 57649 Q96QT6 Y2H
Sakai Y , et al. 2011
PHLDB1 pleckstrin homology-like domain, family B, member 1 23187 Q86UU1 Y2H
Sakai Y , et al. 2011
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H; GST
Sakai Y , et al. 2011
PLEKHA4 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 4 57664 Q9H4M7 Y2H
Sakai Y , et al. 2011
PPHLN1 periphilin 1 51535 Q8NEY8 Y2H
Sakai Y , et al. 2011
PPP1R13L protein phosphatase 1, regulatory (inhibitor) subunit 13 like 10848 Q8WUF5 Y2H
Sakai Y , et al. 2011
PPP1R9B protein phosphatase 1, regulatory (inhibitor) subunit 9B 84687 Q96SB3 Y2H
Sakai Y , et al. 2011
PPP2R3B protein phosphatase 2, regulatory subunit B'', beta 28227 Q9Y5P8 Y2H
Sakai Y , et al. 2011
PRMT2 protein arginine methyltransferase 2 3275 P55345 Y2H
Sakai Y , et al. 2011
PRMT2 protein arginine methyltransferase 2 3275 P55345 IP; LC-MS/MS
Huttlin EL , et al. 2015
PSMD4 proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 5710 P55036 Y2H; GST
Sakai Y , et al. 2011
QSOX1 quiescin Q6 sulfhydryl oxidase 1 5768 O00391 Y2H
Sakai Y , et al. 2011
RBM5 RNA binding motif protein 5 10181 P52756 Y2H
Sakai Y , et al. 2011
Ret ret proto-oncogene 19713 P35546 Y2H; IP/WB
Schuetz G , et al. 2004
RICH2 Rho GTPase-activating protein 44 9912 Q17R89 Y2H
Sakai Y , et al. 2011
RNMTL1 RNA methyltransferase like 1 55178 Q9HC36 Y2H
Sakai Y , et al. 2011
RPL3 ribosomal protein L3 6122 P39023 Y2H
Sakai Y , et al. 2011
RTN3 reticulon 3 10313 O95197 Y2H
Sakai Y , et al. 2011
RUNDC3A RUN domain containing 3A 10900 Q59EK9 Y2H
Sakai Y , et al. 2011
SCYL3 SCY1-like 3 (S. cerevisiae) 57147 Q8IZE3 Y2H
Sakai Y , et al. 2011
SETD2 SET domain containing 2 29072 Q9BYW2 Y2H
Sakai Y , et al. 2011
SFRS9 serine/arginine-rich splicing factor 9 8683 Q13242 Y2H
Sakai Y , et al. 2011
SH3GL2 SH3-domain GRB2-like 2 6456 Q99962 Y2H
Sakai Y , et al. 2011
SH3GL3 SH3-domain GRB2-like 3 6457 Q99963 Y2H
Sakai Y , et al. 2011
SHANK1 SH3 and multiple ankyrin repeat domains 1 50944 Q9Y566 Y2H; IP/WB
Sakai Y , et al. 2011
SHARPIN SHANK-associated RH domain interactor 81858 Q9H0F6 Y2H
Sakai Y , et al. 2011
SIPA1 signal-induced proliferation-associated 1 6494 Q96FS4 Y2H
Sakai Y , et al. 2011
SIRT2 sirtuin 2 22933 Q8IXJ6 Y2H; GST
Sakai Y , et al. 2011
SLC48A1 solute carrier family 48 (heme transporter), member 1 55652 Q6P1K1 Y2H
Sakai Y , et al. 2011
SNRPN small nuclear ribonucleoprotein polypeptide N 6638 P63162 Y2H
Sakai Y , et al. 2011
SORBS2 sorbin and SH3 domain containing 2 8470 O94875 Y2H
Sakai Y , et al. 2011
SORBS3 sorbin and SH3 domain containing 3 10174 O60504 Y2H
Sakai Y , et al. 2011
SPAG5 sperm associated antigen 5 10615 Q96R06 Y2H
Sakai Y , et al. 2011
STK32C serine/threonine kinase 32C 282974 Q86UX6 Y2H
Sakai Y , et al. 2011
SYNGAP1 synaptic Ras GTPase activating protein 1 8831 Q96PV0 Y2H
Sakai Y , et al. 2011
SYT5 synaptotagmin V 6861 O00445 Y2H
Sakai Y , et al. 2011
TCF25 transcription factor 25 (basic helix-loop-helix) 22980 Q9BQ70 Y2H
Sakai Y , et al. 2011
TDRD7 tudor domain containing 7 23424 Q8NHU6 Y2H
Sakai Y , et al. 2011
TFIP11 tuftelin interacting protein 11 24144 Q9UBB9 Y2H
Sakai Y , et al. 2011
THRAP3 thyroid hormone receptor associated protein 3 9967 Q9Y2W1 Y2H
Sakai Y , et al. 2011
TMEM14C transmembrane protein 14C 51522 Q9P0S9 Y2H
Sakai Y , et al. 2011
TNIP2 TNFAIP3 interacting protein 2 79155 Q8NFZ5 Y2H
Sakai Y , et al. 2011
TOP3B topoisomerase (DNA) III beta 8940 O95985 HITS-CLIP
Xu D , et al. 2013
TRAF3 TNF receptor-associated factor 3 7187 Q13114 Y2H
Sakai Y , et al. 2011
TRIM27 tripartite motif-containing 27 5987 P14373 Y2H
Sakai Y , et al. 2011
TRIM9 tripartite motif containing 9 114088 Q9C026 Y2H
Sakai Y , et al. 2011
TRIP10 thyroid hormone receptor interactor 10 9322 Q15642 Y2H
Sakai Y , et al. 2011
TSG101 tumor susceptibility gene 101 7251 Q99816 Y2H
Sakai Y , et al. 2011
TUBA1C tubulin, alpha 1c 84790 Q9BQE3 Y2H
Sakai Y , et al. 2011
UCHL1 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) 7345 P09936 Y2H
Sakai Y , et al. 2011
VIM vimentin 7431 P08670 Y2H
Sakai Y , et al. 2011
VPS18 vacuolar protein sorting 18 homolog (S. cerevisiae) 57617 Q9P253 Y2H
Sakai Y , et al. 2011
WWP1 WW domain containing E3 ubiquitin protein ligase 1 11059 Q9H0M0 Y2H
Sakai Y , et al. 2011
ZCCHC2 zinc finger, CCHC domain containing 2 54877 Q9C0B9 Y2H
Sakai Y , et al. 2011
Cnksr2 connector enhancer of kinase suppressor of Ras 2 245684 Q80YA9 Protein microarray
Stiffler MA , et al. 2006
Dlgap3 discs, large (Drosophila) homolog-associated protein 3 242667 Q6PFD5 ITC; Co-crystal structure; IP/WB; Size-exclusion chromatography (SEC)
Zeng M , et al. 2016
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
GRB2 growth factor receptor-bound protein 2 2885 P62993 IP/WB
Schuetz G , et al. 2004
MED23 Mediator of RNA polymerase II transcription subunit 23 70208 Q80YQ2 MS; IP/WB
Grabrucker S , et al. 2014
MET met proto-oncogene 17295 P16056 IP; LC-MS/MS; Proximity ligation assay
Xie Z , et al. 2016
PAX6 paired box gene 6 18508 P63015 Protein microarray
Stiffler MA , et al. 2006
RALY RNA-binding protein Raly 19383 Q64012 MS; IP/WB
Grabrucker S , et al. 2014
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
ROA0 Heterogeneous nuclear ribonucleoprotein A0 77134 Q9CX86 MS; IP/WB
Grabrucker S , et al. 2014
ROA2 Heterogeneous nuclear ribonucleoproteins A2/B1 102642938 O88569 MS; IP/WB
Grabrucker S , et al. 2014
ROA3 Heterogeneous nuclear ribonucleoprotein A3 229279 Q8BG05 MS; IP/WB
Grabrucker S , et al. 2014
TSC1 tuberous sclerosis 1 64930 Q9EP53 IP/WB
Sakai Y , et al. 2011
Abi1 abl-interactor 1 79249 Q9QZM5 Y2H; GST; IP/WB
Proepper C , et al. 2007
Arhgef7 Rho guanine nucleotide exchange factor (GEF7) 114559 O55043 Y2H; GST; IP/WB
Park E , et al. 2003
Baiap2 BAI1-associated protein 2 117542 Q6GMN2 Y2H; GST; IP/WB
Bockmann J , et al. 2002
Cttn cortactin 60465 Q66HL2 GST; IP/WB
Naisbitt S , et al. 1999
Dbnl drebrin-like 83527 Q9JHL4 GST; IP/WB
Qualmann B , et al. 2004
Dlgap1 discs, large (Drosophila) homolog-associated protein 1 65040 P97836 Y2H; GST; IP/WB
Naisbitt S , et al. 1999
Dlgap2 discs, large (Drosophila) homolog-associated protein 2 116681 P97837 Y2H
Boeckers TM , et al. 1999
Dlgap3 discs, large (Drosophila) homolog-associated protein 3 286923 P97838 Y2H
Boeckers TM , et al. 1999
Dlgap4 discs, large homolog-associated protein 4 (Drosophila) 286930 P97839 Y2H
Boeckers TM , et al. 1999
Grm1 glutamate receptor, metabotropic 1 24414 P23385 GST
Tu JC , et al. 1999
Grm5 glutamate receptor, metabotropic 5 24418 P31424 GST
Tu JC , et al. 1999
HOMER1 homer homolog 1 (Drosophila) 9456 Q86YM7 Y2H; GST; IP/WB
Tu JC , et al. 1999
Homer1 homer homolog 1 (Drosophila) 29456 Q9Z214 Y2H; GST; IP/WB
Tu JC , et al. 1999
Homer2 homer homolog 2 (Drosophila) 29547 O88801 GST
Tu JC , et al. 1999
Homer3 homer homolog 3 (Drosophila) 29548 Q9Z2X5 GST
Tu JC , et al. 1999
Lzts2 leucine zipper, putative tumor suppressor 2 365468 F1LQW9 IP/WB
Schmeisser MJ , et al. 2009
Prosapip1 ProSAPiP1 protein 280670 Q8K1Q4 Y2H; GST; IP/WB
Wendholt D , et al. 2006
Rps6ka3 ribosomal protein S6 kinase polypeptide 3 501560 D3Z8E0 Y2H; IP/WB; WB
Thomas GM , et al. 2005
Shank3 SH3 and multiple ankyrin repeat domains 3 59312 Q9JLU4 GST; IP/WB
Naisbitt S , et al. 1999
Sptan1 spectrin, alpha, non-erythrocytic 1 64159 P16086 Y2H; IP/WB
Bckers TM , et al. 2001
Tbkbp1 TBK1 binding protein 1 266764 Q6DG50 Y2H
Liebau S , et al. 2009
LZTS2 leucine zipper, putative tumor suppressor 2 495421 Q5U4W1 IP/WB
Gessert S , et al. 2011

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