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Relevance to Autism

Several studies have found rare single gene variations in the PTEN gene that have associations with autism, including syndromic associations such as Cowden syndrome (Goffin et al., 2001), where a subpopulation of individuals with the syndrome develop autism.

Molecular Function

The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
PTEN mutation in a family with Cowden syndrome and autism.
Cowden syndrome
ASD
Positive association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Positive Association
Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.
Macrocephaly/autism syndrome
ASD, macrocephaly
Support
Excess of rare, inherited truncating mutations in autism.
ASD
Support
Autistic spectrum disorder in a 9-year-old girl with macrocephaly.
ASD
Support
Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.
ASD
ID, epilepsy
Support
A mutant form of PTEN linked to autism.
Support
Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly.
ASD
DD, epilepsy
Support
Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.
ASD
Support
Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.
ASD, DD, ID
Support
Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.
ASD
Support
A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome.
ID, macrocephaly
Support
The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.
ASD, DD, ID
Support
Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling.
Learning disabilities, macrocephaly
ID
Support
Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.
Cowden syndrome
Support
Novel PTEN mutations in neurodevelopmental disorders and macrocephaly.
ASD
DD, ID
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.
ASD
Support
Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
ASD
Support
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Highly Cited
The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
Highly Cited
PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
Highly Cited
Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.
Recent Recommendation
Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations.
Recent recommendation
Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.
Recent Recommendation
PTEN knockdown alters dendritic spine/protrusion morphology, not density.
Recent recommendation
Functionally distinct groups of inherited PTEN mutations in autism and tumour syndromes.
Recent recommendation
A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.
Recent Recommendation
A secreted PTEN phosphatase that enters cells to alter signaling and survival.
Recent recommendation
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Recent recommendation
Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.
Recent Recommendation
PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.
Recent recommendation
Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.
Recent recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase.
Recent recommendation
PTEN interacts with histone H1 and controls chromatin condensation.
Recent recommendation
The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.
Recent Recommendation
Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.
Recent Recommendation
Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.
Recent recommendation
Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN204R001 
 stop_gained 
 c.534T>G 
 p.Tyr178Ter 
 Familial 
 Maternal 
  
 GEN204R002 
 missense_variant 
 c.278A>G 
 p.His93Arg 
 De novo 
  
 Simplex 
 GEN204R003 
 missense_variant 
 c.755A>G 
 p.Asp252Gly 
 De novo 
  
 Simplex 
 GEN204R004 
 missense_variant 
 c.722T>C 
 p.Phe241Ser 
 De novo 
  
 Simplex 
 GEN204R005 
 5_prime_UTR_variant 
 c.-1088C>T 
  
  
  
  
 GEN204R006 
 5_prime_UTR_variant 
 c.-1048C>T 
  
 Familial 
 Maternal 
 Multiplex 
 GEN204R007 
 5_prime_UTR_variant 
 c.-1026C>A 
  
 Familial 
 Maternal 
  
 GEN204R008 
 5_prime_UTR_variant 
 c.-903G>A 
  
  
  
  
 GEN204R009 
 5_prime_UTR_variant 
 c.-903G>A 
  
  
  
  
 GEN204R010 
 missense_variant 
 c.66C>G 
 p.Asp22Glu 
 Familial 
 Paternal 
 Multiplex 
 GEN204R011 
 intron_variant 
 T to C 
 N/A 
 Familial 
 Maternal 
  
 GEN204R012 
 missense_variant 
 c.976G>A 
 p.Asp326Asn 
 De novo 
  
  
 GEN204R013 
 stop_gained 
 c.1003C>T 
 p.Arg335Ter 
 De novo 
  
  
 GEN204R014 
 missense_variant 
 c.232A>G 
 p.Thr78Ala 
 De novo 
  
 Simplex 
 GEN204R015 
 missense_variant 
 c.618C>G 
 p.Phe206Leu 
 Unknown 
  
 Simplex 
 GEN204R016 
 copy_number_loss 
 delTTAGT 
 N/A 
 Unknown 
  
 Simplex 
 GEN204R017 
 missense_variant 
 c.500C>A 
 p.Thr167Asn 
 De novo 
  
 Simplex 
 GEN204R018 
 missense_variant 
 c.392C>T 
 p.Thr131Ile 
 De novo 
  
 Simplex 
 GEN204R019 
 frameshift_variant 
 c.405dupA 
 p.Cys136MetfsTer44 
 De novo 
  
 Simplex 
 GEN204R020 
 stop_gained 
 c.640C>T 
 p.Gln214Ter 
 Familial 
 Maternal 
 Simplex 
 GEN204R021 
 missense_variant 
 c.402G>C 
 p.Met134Ile 
 Familial 
 Maternal 
 Multi-generational 
 GEN204R022 
 frameshift_variant 
 c.420_421insA 
 p.His141ThrfsTer39 
 Unknown 
  
 Unknown 
 GEN204R023 
 missense_variant 
 c.208C>G 
 p.Leu70Val 
 Unknown 
  
 Unknown 
 GEN204R024 
 initiator_codon_variant 
 c.3G>T 
 p.Met1Ile 
 Unknown 
  
 Unknown 
 GEN204R025 
 stop_gained 
 c.1003C>T 
 p.Arg335Ter 
 Unknown 
  
 Unknown 
 GEN204R026 
 splice_site_variant 
 c.209 + 5G>A 
  
 Unknown 
  
 Unknown 
 GEN204R027 
 missense_variant 
 c.737C>T 
 p.Pro246Leu 
 De novo 
  
  
 GEN204R028 
 frameshift_variant 
 c.43delA 
 p.Arg15AspfsTer9 
 Unknown 
  
  
 GEN204R029 
 splice_site_variant 
 c.493-1G>A 
  
 De novo 
  
 Simplex 
 GEN204R030 
 frameshift_variant 
 c.619delA 
 p.Ser207ValfsTer14 
 Unknown 
  
 Unknown 
 GEN204R031 
 missense_variant 
 c.400A>T 
 p.Met134Leu 
 Unknown 
  
 Unknown 
 GEN204R032 
 missense_variant 
 c.353A>C 
 p.His118Pro 
 De novo 
  
  
 GEN204R033 
 missense_variant 
 c.527A>G 
 p.Tyr176Cys 
 De novo 
  
  
 GEN204R034 
 missense_variant 
 c.827A>G 
 p.Asn276Ser 
 De novo 
  
  
 GEN204R035 
 stop_gained 
 c.338C>T 
 p.Arg130Ter 
 Familial 
 Paternal 
 Multi-generational 
 GEN204R036 
 missense_variant 
 c.470A>G 
 p.Glu157Gly 
 De novo 
  
 Multiplex (identical twins) 
 GEN204R037 
 stop_gained 
 c.416T>A 
 p.Leu139Ter 
 Familial 
 Paternal 
 Simplex 
 GEN204R038 
 frameshift_variant 
 c.520insT 
  
 De novo 
  
  
 GEN204R039 
 intron_variant 
 C>G 
  
 De novo 
  
  
 GEN204R040 
 missense_variant 
 c.131G>A 
 p.Gly44Asp 
 Unknown 
  
 Unknown 
 GEN204R041 
 missense_variant 
 c.518G>A 
 p.Arg173His 
 Familial 
 Maternal 
 Multi-generational 
 GEN204R042 
 missense_variant 
 c.605C>T 
 p.Thr202Ile 
 De novo 
  
  
 GEN204R043 
 splice_site_variant 
 G>A 
  
 Unknown 
  
  
 GEN204R044 
 stop_gained 
 c.697C>T 
 p.Arg233Ter 
 Unknown 
 Not paternal 
 Multi-generational 
 GEN204R045 
 splice_site_variant 
 A>G 
  
 Familial 
 Paternal 
 Multi-generational 
 GEN204R046 
 missense_variant 
 c.369C>G 
 p.His123Gln 
 Unknown 
  
 Unknown 
 GEN204R047 
 missense_variant 
 c.518G>A 
 p.Arg173His 
 Familial 
 Paternal 
 Multi-generational 
 GEN204R048 
 missense_variant 
 c.821G>T 
 p.Trp274Leu 
 Familial 
 Maternal 
 Multi-generational 
 GEN204R049 
 missense_variant 
 c.401T>C 
 p.Met134Thr 
 Familial 
 Maternal 
 Multi-generational 
 GEN204R050 
 inframe_insertion 
 c.239-21G>C 
  
 De novo 
  
 Simplex 
 GEN204R051 
 missense_variant 
 c.274G>A 
 p.Asp92Asn 
 De novo 
  
 Simplex 
 GEN204R052 
 missense_variant 
 c.494G>T 
 p.Gly165Val 
 De novo 
  
  
 GEN204R053 
 missense_variant 
 c.[545T>C];[545T>C] 
 p.[Leu182Ser];[Leu182Ser] 
 Familial 
 Both parents 
 Multiplex 
 GEN204R054 
 stop_gained 
 c.195C>A 
 p.Tyr65Ter 
 Unknown 
  
 Unknown 

Common

No Common Variants Available



Model Summary

Mutant mice display abnormal social interaction and exaggerated responses to sensory stimuli.

External Links

AllenBrainAtlas   MGI Logo  Entrez Gene

References

Type
Title
Author, Year
Primary
Pten regulates neuronal arborization and social interaction in mice.
Primary
Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice.
Additional
Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: interplay between Pten and p53.
Additional
Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism.
Additional
Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests.
Additional
Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.
Additional
Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.
Additional
Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.
Additional
The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles.
Additional
Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.

PTEN_1_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Cre-LoxP mediated conditional deletion of Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus, Nse-Cre transgene
Allele Type: Conditional (knockout)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: E14K
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_2_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Cre-loxP mediated deletion of exon 5 of Pten specifically in neural tissues, Nse-Cre transgene
Allele Type: Conditional (knockout)
Strain of Origin: BALB/c
Genetic Background: C57BL/6
ES Cell Line: 129S4/SvJae
Mutant ES Cell Line: Not Specified
Model Source: Not specified

PTEN_3_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Cre-loxP mediated deletion of Pten gene in granule cells of dentate gyrus and pyramidal neurons of hippocampal CA3 and a subset of postmitotic neruons in the cortex as well, using Nse-Cre transgene
Allele Type: Conditional (knockout)
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_6_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Deletion of gene sequence from BglII site in exon 5 to the next BglII site 2.0 kb downstream
Allele Type: Targeted (knockout)
Strain of Origin: 129Sv/J
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_7_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 5 of Pten is flanked by loxP sites; Cre transgene targeted to endogenous Slc6a3 (Dopamine transporter, DAT) promoter
Allele Type: Conditional (knockout)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_4_KI_ M3M4_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: M3M4 missense double mutations were targeted into the Pten exon 7, which contains the NLS-like sequence
Allele Type: Targeted (knockin)
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_5_KI_M3M4_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: M3M4 missense double mutations were targeted into the Pten exon 7, which contains the NLS-like sequence
Allele Type: Targeted (knockin)
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_8_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 5 of Pten is flanked by loxP sites; Cre transgene construct under T2A element coexpressed with fluorescent reporter in replication-deficient retrovirus was injected bilaterally into dentate gyrus at postnatal day 7
Allele Type: Conditional (knockout)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

PTEN_10_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A conditional homozygous knock out of PTEN (floxed Exon4 - 5) was generated by breeding Pten flox/flox mice with the Dlxl12b-cre mice. This results in the knock out of Pten from the secondary progenitor cells of the subventricular zone of the subpallium, by E15.5. The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_11_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A conditional homozygous knock out of PTEN (floxed Exon4 - 5) was generated by breeding Pten flox/flox mice with SST-IRES-Cre mice. This results in the knock out of Pten from postmitotic SST+ cells as they leave the MGE. The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1* C56BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_12_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: In this conditional, cell transplant based model, cells from the from the complex crossing of Pten flox/flox : Dlxl12b-Cre+:Ai14flox/+ background from E12.5 embryos were transplanted to wild type recipient mice at P1. The recipient mouse neocortices were then examined 35 days following transplantation.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_13_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A conditional heterozygous knock out of PTEN (floxed Exon4 - 5) was generated by breeding Pten flox/flox mice with the Nkx2.1-Cre (bac transgenic) mice. This results in the knock out of Pten from the ventricular zone of the medical ganglionic eminence (MGE) starting E9.5 also resulting in these het mice. The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_14_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A conditional heterozygous knock out of PTEN (floxed Exon4 - 5) was generated by breeding Pten flox/flox mice the Dlxl12b-cre mice.This results in the knock out of Pten from the secondary progenitor cells of the subventricular zone of the subpallium, by E15.5, het mice are also obtained as littermates . The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_15_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A conditional heterozygous knock out of PTEN (floxed Exon4 - 5) was generated by breeding Pten flox/flox mice with SST-IRES-Cre mice. This results in the knock out of Pten from postmitotic SST+ cells as they leave the MGE, and het mice are also obtained as littermates. The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_16_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: In this conditional, cell transplant based model, cells from the from the complex crossing of Pten flox/+ : Dlxl12b-Cre+:Ai14flox/+ background from E12.5 embryos were transplanted to wild type recipient mice at P1. The recipient mouse neocortices were then examined 35 days following transplantation.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_9_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A conditional homozygous knock out of PTEN (floxed Exon4 - 5) was generated by breedingPten flox/flox mice with the Nkx2.1-Cre (bac transgenic) mice. This results in the knock out of Pten from the ventricular zone of the medical ganglionic eminence (MGE) starting E9.5. The tdtomato reporter under Ai14 Flox/+ line was used to follow expression of the cre recombinase.
Allele Type: Conditional(knockout) ; Reporter
Strain of Origin: CD1* C56BL/6
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_17_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 5 of the Pten gene was targeted to be flanked with LoxP sites. Mice homozygous for floxed exon5 Pten fl/fl were crossed with L7/Cre transgenic mice that express cre recombinase under the L7 promoter primarily in the Purkinje cells of the cerebellum only
Allele Type: Conditional(knockout)
Strain of Origin:
Genetic Background: C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

PTEN_1_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Abnormal
Description: Abnormal Locomotor Activity; Hyperactive in light boxes, normal in dark boxes
Exp Paradigm: Open field test
 Open field test
 6 weeks
Dendritic spine density and architecture1
Abnormal
Description: Dendritic hypertrophy, ectopy, and increased spine density in cerebral cortex and dentate gyri
Exp Paradigm: Golgi staining; Immunohistochemistry with antibodies to dendritic markers; Electron microscopic analysis of cortex and dentate gyri
 Immunohistochemistry
 3-9 months
Brain morphology1
Abnormal
Description: Progressive macrocephaly in forebrain; foliation of DG and compression of CA1; increased neuronal size with soma hypertrophy
Exp Paradigm: General Observation; Hematoxylin/Eoslin staining on coronal sections
 Histology: H&E staining
 Unreported
Synapse density1
Abnormal
Description: Hypertrophic and ectopic axonal tract with increased synapses in Dentate Gyrus
Exp Paradigm: Immunohistochemistry with antibodies to synapsin (presynaptic marker) and calbindin (expressed in soma and processes); Electron microscopic analysis of the inner molecular layer of dentate gyri
 Immunohistochemistry
 10.7 months
Seizures1
Abnormal
Description: Sporadic Seizure propensity during light phase; Repetitive spike-wave patterns with continous spike-wave bursting
Exp Paradigm: Subjective Observation; Analysis of EEG/EMG recordings of mice
 Observation of seizures; Electroencephalogram/electromyogram (EEG/EMG)
 3-9 months
Sensorimotor gating1
Abnormal
Description: Significantly impaired startle response
Exp Paradigm: Prepulse inhibition of the acoustic startle response as a measure of sensorimotor gating.
 Prepulse inhibition
 6 weeks
Acoustic startle reflex1
Increased
Description: Increased Startle Reflex with habituation to repeated stimuli
Exp Paradigm: Response to 120 dB white noise stimulus
 Acoustic startle reflex test: 120 dB white noise stimulus
 6 weeks
Social approach1
Decreased
Description: Decreased social approach
Exp Paradigm: Social preference test in tripartite chamber
 Three-chamber social approach test
 Unreported
Social interaction1
Decreased
Description: Decreased social interaction
Exp Paradigm: Social interaction between social target and empty cage in open field
 Reciprocal social interaction test
 Unreported
Nest building behavior1
Decreased
Description: Decreased nest building activity
Exp Paradigm: Nest forming test for home cage behavior
 Nest building assay
 Unreported
Social interaction1
Decreased
Description: Decreased social interaction
Exp Paradigm: Direct contacts between genotypically identical test
 Reciprocal social interaction test
 Unreported
Social transmission of food preference1
Decreased
Description: Decreased social learning
Exp Paradigm: Direct contacts between genotypically identical test
 Reciprocal social interaction test
 Unreported
Anxiety1
Increased
Description: Increased anxiety-like behavior
Exp Paradigm: Open field test; Dark/Light apparatus
 Open field test; Light-dark exploration test
 Unreported
Spatial reference memory1
Decreased
Description: Decreased rate of acquisition of Spatial Reference Memory
Exp Paradigm: Morris water maze task
 Morris water maze test
 Unreported
Nursing/lactation1
Abnormal
Description: Abnormal maternal nursing
Exp Paradigm: Pup survival rate
 Survival analysis: pups
 Unreported
Protein modification process1
Increased
Description: Increased phosphorylation of downstream targets of Pten such as P-Akt, P-S6, P-Gsk3, Tuberin
Exp Paradigm: Downstream Targets Phosphorylation
 Immunohistochemistry
 2 months
General characteristics1
 No Change
 General observations
 4-5 weeks
Anxiety1
 No Change
 Elevated plus maze test
 Unreported
Cued or contextual fear conditioning: Memory of cue1
 No Change
 Fear conditioning test: contextual and acoustic cue-dependent
 Unreported
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Unreported
Motor strength and endurance1
 No Change
 Vertical pole test; Dowel walk test
 Unreported
Olfaction1
 No Change
 Buried food test
 Unreported
Inanimate object preference1
 No Change
 Three-chamber social approach test: sociability
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Neurophysiology, Repetitive behavior

PTEN_2_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain size1
Increased
Description: Increased enlargement of cortex and hippocampus over cerebellum
 
 5-7 months
Brain size1
Increased
Description: Increased brain weight (normalized to body weight)
 
 5-7 months
Self grooming: perseveration1
Increased
Description: Increased self grooming indicated by twice the frequency of self grooming
Exp Paradigm: Observation of self-grooming activities
 Grooming behavior assessments
 5-7 months
Social interaction1
Decreased
Description: Decreased sociability demonstrated by decreased time spent with social target with same number of entries towards social side and decreased time spent sniffing social target with No Change in sniff frequency
Exp Paradigm: Socialization trial with measures of number of entires and time spent in each side of box, and time spent sniffing each wire cage
 Three-chamber social approach test: sociability
 5-7 months
Social interaction1
Decreased
Description: Decreased social novelty as demonstrated by lower novel to total side time ratio and lower time spent sniffing novel mouse normalized by total sniff time
Exp Paradigm: Social novelty preference trial
 Three-chamber social approach test: social novelty
 5-7 months
Oxidative stress: systemic1
Increased
Description: Increased nitrative/oxidative stress indicated by increased nitrated Tyr in ATPase beta-subunit
Exp Paradigm: Mitochondrial enzymaic and complex activity measurement from isolated mitochondria from hippocampus and cerebellum
 Mitochondrial respiratory chain enzyme analysis
 5-6 months
Protein expression level evidence1
Decreased
Description: Decreased p53 protein expression in cerebellum
Exp Paradigm: P53 Protein Expression
 Western blot
 5-7 months
Signaling1
Decreased
Description: Decreased levels of p21, SCO2 in cerebellum and hippocampus
Exp Paradigm: P53 Downstream Effectors Levels
 Western blot
 5-7 months
Mitochondrial DNA replication1
Increased
Description: Increased mtDNA copy number in cerebellum
Exp Paradigm: Mtdna Copy Number
 Quantitative PCR (qRT-PCR)
 8-13 weeks
Protein expression level evidence1
Increased
Description: Increased levels of glial fibrillary acidic protein
Exp Paradigm: Gfap Protein Levels
 Western blot
 5-7 months
Enzyme activity1
Decreased
Description: Decreased cytochrome c oxidase activity in cerebellum and hippocampus
Exp Paradigm: Cytochrome C Oxidase Activity
 Mitochondrial respiratory chain enzyme analysis
 5-7 months
Protein expression level evidence1
Decreased
Description: Decreased levels of Pten protein expression in hippocampus and cerebellum
Exp Paradigm: Pten Protein Expression
 Western blot
 4-29 weeks
Enzyme activity1
 No Change
 Mitochondrial respiratory chain enzyme analysis
 4-29 weeks
Mitochondrial biogenesis1
 No Change
 Mitochondrial respiratory chain enzyme analysis
 4-6 weeks
Mitochondrial biogenesis1
 No Change
 Mitochondrial respiratory chain enzyme analysis
 8-13 weeks
Protein expression level evidence1
 No Change
 Western blot
 8-13 weeks
Protein expression level evidence1
 No Change
 Western blot
 4-29 weeks
Protein expression level evidence1
 No Change
 Western blot
 4-6 weeks
Protein expression level evidence1
 No Change
 Western blot
 4-29 weeks
Self grooming: perseveration1
 No Change
 Grooming behavior assessments: self grooming
 8-13 weeks
Social interaction1
 No Change
 Three-chamber social approach test: sociability
 8-13 weeks
Social interaction1
 No Change
 Three-chamber social approach test: social novelty
 8-13 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Seizure, Sensory

PTEN_3_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain morphology1
Abnormal
Description: Abnormal brain morphology indicated by enlarged DGC and hypertrophied mossy fiber projection axons
Exp Paradigm: H&E Staining
 Histology: H&E staining
 5 months
Synaptic plasticity1
Decreased
Description: Decreased synaptic plasticity as assessed through mGluR-LTD at DGC synapses
Exp Paradigm: Whole cell recordings in the medial prefrontal pathway
 Whole-cell patch clamp
 2-7.5 months
Synaptic plasticity1
Increased
Description: Increased synaptic plasticity as assessed by TBS-LTP at DGC synapse
Exp Paradigm: Whole cell recordings in the medial prefrontal pathway
 Whole-cell patch clamp
 8-12 weeks
Presynaptic function: paired-pulse facilitation1
Decreased
Description: Decreased presynaptic function as measured by paired pulse ratio (PPR) at DGC synapse
Exp Paradigm: Whole cell recordings in the medial prefrontal pathway
 Whole-cell patch clamp
 3.5-5 months
Synaptic plasticity1
Decreased
Description: Decreased synaptic plasticity as assessed through TBS-LTP and HFS-LTP at CA3-CA1 synapses
Exp Paradigm: Whole cell recordings at CA3-CA1 synapses
 Whole-cell patch clamp
 4-5months
Synaptic transmission1
Increased
Description: Increased basal synaptic transmission as measured with input/output relation at DGC synapse
Exp Paradigm: Whole cell recordings in the medial prefrontal pathway
 Whole-cell patch clamp
 3.5-5 months
Synaptic plasticity1
Decreased
Description: Decreased synaptic plasticity as assessed by impaired TBS-LTP at DGC synapses
Exp Paradigm: Whole cell recordings in the medial prefrontal pathway
 Whole-cell patch clamp
 3.5-7.5 months
Protein expression level evidence1
Decreased
Description: Decreased expression of Pten in DGC and CA3 pyramidal cells
Exp Paradigm: Pten Protein Expression
 Immunohistochemistry
 8 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp
 8-30 weeks
Synaptic plasticity1
 No Change
 Whole-cell patch clamp
 8-20 weeks
Synaptic plasticity1
 No Change
 Whole-cell patch clamp
 8-12 weeks
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 8-20 weeks
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 8-30 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_6_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Locomotor activity in diurnal cycle2
Decreased
Description: In females, decreased activity during light hours, with fewer rotations
Exp Paradigm: Wheel running monitoring
 Wheel running monitoring
 7-20 weeks
Locomotor activity in the dark2
Decreased
Description: In females, decreased overall activity during dark hours, with fewer rotation but with increased bouts of activity
Exp Paradigm: Wheel running monitoring
 Wheel running monitoring
 7-20 weeks
Locomotor activity in diurnal cycle2
Increased
Description: In males, a slight increase in activity in light hours
Exp Paradigm: Wheel running monitoring
 Wheel running monitoring
 7-20 weeks
Brain morphology2
Abnormal
Description: Overgrowth in anterior and posterior halves of cortex, in the cerebellum and in the remainder of the brain; only males reported
Exp Paradigm: Measurement of tissue weight
 Measurement of tissue weight
 7-20 weeks
Brain size2
Increased
Description: Greater absolute and relative brain mass; both sexes reported, analyzed separately
Exp Paradigm: Brain weighed, body weighed
 General observations
 7-20 weeks
Repetitive digging2
Increased
Description: In males, increased digging behavior
Exp Paradigm: Marble-burying test
 Marble-burying test
 7-20 weeks
Self grooming: perseveration1
Increased
Description: In males, increased self-grooming behavior
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Repetitive digging1
Increased
Description: In males, increased digging behavior
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Rearing behavior1
Increased
Description: In males, increased vertical exploratory activity
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Social habituation2
Decreased
Description: In males, decreased social habituation, compared to male controls
Exp Paradigm: Reciprocal social interaction test: confined stimulus mouse: juvenile conspecific P21-P28, four 5-minute stimulus presentations, 10-minute intertrial intervals
 Reciprocal social interaction test: confined stimulus mouse
 7-20 weeks
Social memory2
Decreased
Description: Decreased preference for novel social stimulus; both sexes reported, analyzed separately
Exp Paradigm: Three-chamber social approach test
 Three-chamber social approach test: social novelty
 7-20 weeks
Aggression1
Decreased
Description: In males, residents exhibit less dominance scores, have fewer discrete attacks, spend less time fighting, and have a greater latency to attack
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Social approach2
Decreased
Description: Decreased preference for social stimulus; both sexes reported, analyzed separately
Exp Paradigm: Three-chamber social approach test
 Three-chamber social approach test: sociability
 7-20 weeks
Social interaction1
Decreased
Description: In males, decreased duration and frequence of solcial behavor
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Depression2
Increased
Description: In males, increased immobility in the tail suspension test and the forced swim test
Exp Paradigm: Tail suspension test; Forced swim test
 Tail suspension test; Forced swim test
 7-20 weeks
Exploratory activity1
Increased
Description: In males, increased horizontal exploratory activity
Exp Paradigm: Resident-intruder test: 15-minute interaction
 Resident-intruder test
 11-16 weeks
Anxiety2
Decreased
Description: In males, decreased latency to light compartment, increased number of crossings between light and dark, more time spent in light compartment, more time spent in center of open field
Exp Paradigm: Light-dark exploration test; Open field test
 Light-dark exploration test; Open field test
 7-20 weeks
Cued or contextual fear conditioning: Memory of context2
Decreased
Description: In females, decreased freezing behavior when testing context
Exp Paradigm: Fear conditioning test: trace
 Fear conditioning test: trace
 7-20 weeks
Cued or contextual fear conditioning: Trace fear conditioning2
Decreased
Description: In females, decreased freezing behavior when testing auditory cue
Exp Paradigm: Fear conditioning test: trace
 Fear conditioning test: trace
 7-20 weeks
Circadian rhythms: timing/phases of locomotor activity2
 No Change
 Wheel running monitoring: constant dark conditions
 7-20 weeks
Locomotor activity in the dark2
 No Change
 Wheel running monitoring
 7-20 weeks
Size/growth2
 No Change
 General observations
 7-20 weeks
Anxiety2
 No Change
 Light-dark exploration test; Open field test
 7-20 weeks
Depression2
 No Change
 Tail suspension test; Forced swim test
 7-20 weeks
Cued or contextual fear conditioning: Memory of context2
 No Change
 Fear conditioning test: trace
 7-20 weeks
Cued or contextual fear conditioning: Trace fear conditioning2
 No Change
 Fear conditioning test: trace
 7-20 weeks
General locomotor activity: Ambulatory activity2
 No Change
 Three-chamber social approach test; Open field test
 7-20 weeks
Motor coordination and balance2
 No Change
 Accelerating rotarod test
 7-20 weeks
Repetitive digging2
 No Change
 Marble-burying test
 7-20 weeks
Pain or nociception2
 No Change
 Hot plate test
 7-20 weeks
Social dishabituation2
 No Change
 Reciprocal social interaction test: confined stimulus mouse
 7-20 weeks
Social habituation2
 No Change
 Reciprocal social interaction test: confined stimulus mouse
 7-20 weeks
Social interaction2
 No Change
 Reciprocal social interaction test: confined stimulus mouse
 7-20 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure, Sensory

PTEN_7_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: Ambulatory activity1
Abnormal
Description: In males, decreased distance traveled during sociability test but not during social novelty test
Exp Paradigm: Three-chamber social approach test
 Three-chamber social approach test
 7-15 weeks
Social memory1
Decreased
Description: In males, no preference for novel social stimulus, compared to controls
Exp Paradigm: Three-chamber social approach test: social novelty
 Three-chamber social approach test: social novelty
 7-15 weeks
Social approach1
Decreased
Description: In females, decreased preference for social stimulus
Exp Paradigm: Three-chamber social approach test: sociability
 Three-chamber social approach test: sociability
 7-15 weeks
General locomotor activity: Ambulatory activity1
 No Change
 Three-chamber social approach test
 7-15 weeks
Social approach1
 No Change
 Three-chamber social approach test: sociability
 7-15 weeks
Social memory1
 No Change
 Three-chamber social approach test: social novelty
 7-15 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

PTEN_4_KI_ M3M4_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Myelination1
Increased
Description: Increased ratio of corpus callosum thickness to cortical thickness, compared to wild-types and heterozygotes
Exp Paradigm: Immunohistochemistry: MBP for corpus callosum, NeuN for cortex
 Immunohistochemistry
 6 weeks
Morphology and size of the corpus callosum1
Increased
Description: Increased corpus callosum thickness compared to wild type and heterozygote
Exp Paradigm: Immunohistochemistry: MBP for corpus callosum, NeuN for cortex
 Immunohistochemistry
 6 weeks
Gene expression1
Abnormal
Description: Differential expression of genes related to myelanation, the majority of which were upregulated; out of all differentially expressed genes there is a significant enrichment in myelination-related genes
Exp Paradigm: RNA sequencing of cortical tissue followed by pathway and gene ontology analysis of differentially expressed genes
 RNA sequencing
 6 weeks
Cortical thickness1
 No Change
 Immunohistochemistry
 6 weeks
 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

PTEN_5_KI_M3M4_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Morphology and size of the corpus callosum1
Increased
Description: Increased corpus callosum thickness compared to wild type
Exp Paradigm: Immunohistochemistry: MBP for corpus callosum, NeuN for cortex
 Immunohistochemistry
 6 weeks
Myelination1
Increased
Description: Increased ratio of corpus callosum thickness to cortical thickness, compared to wild-types
Exp Paradigm: Immunohistochemistry: MBP for corpus callosum, NeuN for cortex
 Immunohistochemistry
 6 weeks
Cortical thickness1
 No Change
 Immunohistochemistry
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_8_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic spine density and architecture: dendritic tree complexity1
Increased
Description: Increased primary dendrites, number of branching points, number of distal branches, total surface area and dendritic volume
Exp Paradigm: Fluorescence microscopy
 Fluorescence microscopy
 3-4.5 weeks
Dendritic spine density and architecture1
Increased
Description: Increased filopodial density, mushroom spine density, and number of spine maturation events
Exp Paradigm: Fluorescence microscopy
 Fluorescence microscopy
 3-4.5 weeks
Synapse density: Excitatory1
Increased
Description: Increased number of quantal fractions (aEPSCs) that fit in an evoked EPSC
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Brain cytoarchitecture1
Increased
Description: Increased soma size of neurons with Pten deletion
Exp Paradigm: Immunohistochemistry: Pten; Fluorescence microscopy
 Immunohistochemistry; Fluorescence microscopy
 3-4.5 weeks
Dendritic spine density and architecture1
Increased
Description: Increased protusion density, increased dendritic caliber
Exp Paradigm: Fluorescence microscopy
 Fluorescence microscopy
 3-4.5 weeks
Action potential firing1
Increased
Description: Increased threshold of current delivered to afferent stimulation to fire action potential, increased spike amplitude, more active spike rate
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Ion influx and permeability: Calcium1
Increased
Description: Neurons have greater calcium transients
Exp Paradigm: Fluorescence microscopy
 Fluorescence microscopy
 3-4.5 weeks
Miniature post synaptic current frequency: excitatory1
Increased
Description: Increased frequency of miniature EPSCs
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Neuronal activation1
Increased
Description: Increased neuronal activation of neurons with Pten deletion, measured as an increase of phospho-S6
Exp Paradigm: Immunohistochemistry: phospho-S6; Fluorescence microscopy
 Immunohistochemistry; Fluorescence microscopy
 3-4.5 weeks
Synaptic transmission: excitatory1
Increased
Description: Increased amplitude of evoked AMPA EPSCs
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Intrinsic membrane properties1
Abnormal
Description: Increase capacitance, decreased input resistance, increased threshold to fire action potential
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Miniature post synaptic current amplitude: excitatory1
Increased
Description: Increased amplitude of miniature EPSCs
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Network excitability1
Increased
Description: Developing granule neurons are more sensitive to to afferent stimulation
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Neurotransmitter release: quantal parameters1
Increased
Description: Small increase of asynchronous EPSCs, which represent quantal fractions
Exp Paradigm: Whole-cell patch clamp
 Whole-cell patch clamp
 3-4.5 weeks
Targeted protein expression1
Decreased
Description: Null expression of Pten in neurons infected with retrovirus containing Cre, compared to control without Cre
Exp Paradigm: Immunohistochemistry: Pten; Fluorescence microscopy
 Immunohistochemistry; Fluorescence microscopy
 2 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp
 3-4.5 weeks
Synaptic transmission: inhibitory1
 No Change
 Whole-cell patch clamp
 3-4.5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_10_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
Decreased
Description: The reduction in interneuronal number is biased towards loss of somatostatin (SST) expressing interneurons in the cortex, the ratio of SST/PV expressing interneurons is signficantly reduced.
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 P18
Anatomical projections and connectivity1
Increased
Description: The neuropils of the Parvalbumin +ve neurons extend upto Layer I, unlike in WT controls where these projections remain within layerII to VI in mice with Pten cKO homozygous for sub ventricular zone (SVZ) derived interneurons
 Fluorescence microscopy; Immunohistochemistry
 P18
Neuronal number: Interneurons1
Decreased
Description: There is a very significant decrease in the number of interneurons in the Pten cKO homozygous mice, that are believed to be the lineage of the Dlxl12b-cre expressing cells. There is an overall reduction of 53% in total number of interneurons in these mouse brains as well
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 P18
Mortality/lethality1
Increased
Description: The loss of Pten from the secondary progenitors of the sub ventricular zone in this model leads to increased mortality as the mice die after P18
 
 P18
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_11_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Anatomical projections and connectivity1
 No Change
 Fluorescence microscopy; Immunohistochemistry
 4 weeks
Neuronal number: Interneurons1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_12_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain cytoarchitecture1
Increased
Description: There is also an increase in the soma size of the transplanted Pten cKO cells, indicating it a cell autonomous phenotype
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 35DPT
Neuronal differentiation and specification in the brain1
Decreased
Description: The transplanted cells lacking Pten (Pten cKO MGE cells) recapitulate the phenotype of the donor mice, and have significant reduction in somatostatin expressing interneurons that develop from the Pten cKO progenitor cells and there is a significant reduction in the ratio of SST/ PV expressing interneurons that develop from the transplants
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 35DPT
Intrinsic membrane properties1
Decreased
Description: The resting membrane potential and the action potential threshold is significantly reduced in the transplanted Pten cKO neurons present in the brain of WT mice
 Whole-cell patch clamp
 45DPT
Action potential firing1
 No change
 Whole-cell patch clamp
 45DPT
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_13_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mortality/lethality1
 No change
 
 
Size/growth1
 No change
 Body weight measurement
 4 weeks
Anatomical projections and connectivity1
 No change
 Fluorescence microscopy; Immunohistochemistry
 4 weeks
Brain size1
 No change
 
 4 weeks
Neuronal differentiation and specification in the brain1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
Spontaneous post synaptic events: inhibitory currents1
 No change
 Whole-cell patch clamp
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_14_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
Neuronal number: Interneurons1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_15_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 P18
Neuronal number: Interneurons1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 P18
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_16_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
Decreased
Description: Heterozygous Pten cKO in MGE derived progenitors show decrease in the number of somatostatin expressing interneurons arising from the transplants
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
Brain cytoarchitecture1
 No change
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

PTEN_9_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain cytoarchitecture1
Increased
Description: The cell/soma size of interneurons that have homozygous loss of Pten is significantly increased.
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 
Neuronal differentiation and specification in the brain1
Decreased
Description: There is also a reduction in SST expressing interneurons in the sgtraituma s well.
 Fluorescence microscopy; Immunohistochemistry:striatum; Cell counting
 4 weeks
Neuronal number: Interneurons1
Decreased
Description: There is a very significant decrease in the number of interneurons in the Pten cKO homozygous mice, that are believed to be the lineage of the Nkx2.1-cre expressing cells. There is an overall reduction of 53% in total number of interneurons, a majority of which occurs in between P0 and P8.
 Fluorescence microscopy; Immunohistochemistry; Cell counting
 P0, P8, 4 weeks
Neuronal differentiation and specification in the brain1
Decreased
Description: The reduction in interneuronal number is biased towards loss of somatostatin (SST) expressing interneurons in the cortex, it is first detectable staring E15.5 and continues to be significant through P30. The ratio of SST/PV expressing interneurons is signficantly reduced.
 Fluorescence microscopy; Immunohistochemistry: cortex; Cell counting
 E15.5, 4 weeks
Neuronal differentiation and specification in the brain1
Decreased
Description: There is reduction in SST expressing interneurons in the hippocampus as well.
 Fluorescence microscopy; Immunohistochemistry: hippocampus; Cell counting
 4 weeks
Anatomical projections and connectivity1
Increased
Description: The neuropils of the Parvalbumin +ve neurons extend upto Layer I, unlike in WT controls where these projections remain within layerII to VI in mice with Pten cKO (homozygous) MGE derived interneurons
 
 4 weeks
Apoptosis: brain cells1
Increased
Description: There is a significant increase in the expression of cleaved caspase3(cC3), an apoptopis marker,in the MFE derived interneurons of the neocortex and lateral cortex marginal zone (Nkx2.1-cre/ tdtomato marker expressing). By P0 about 36% of the Pten cKO homozygous cells express cC3.
 Expression of cleaved caspase-3 (cC3); Fluorescence microscopy; Immunohistochemistry; Cell counting
 E17.5, P0
Spontaneous post synaptic events: inhibitory currents1
Increased
Description: There is a two fold increase in the frequency of spontaneous IPScs ONTO layer II/III excitatory neurons that are connected to the MGE derived interneurons (Pten cKO, homozygous in this model)
 Whole-cell patch clamp
 4 weeks
Apoptosis: brain cells1
Increased
Description: The interneurons that express somatostatin and are Pten cKO homozygous, have a much higher probability of expressing cleaved caspace3
 Immunohistochemistry: SST; Fluorescence microscopy; Expression of cleaved caspase-3 (cC3); Cell counting
 P0
Electroencephalogram (EEG) signature1
Increased
Description: The Pten ckO homozygous interneurons had an elevated EGG power during behavioral testing in the reciproal social interaction in the gamma frequency band
 Electroencephalogram (EEG): gamma oscillations; Reciprocal social interaction test
 4 weeks
Social interaction1
Decreased
Description: Mice with Pten cKO homozygous MGE derived interneurons have significantly reduced preference for a novel mouse compared to control mice
 Reciprocal social interaction test
 P30
Size/growth1
Decreased
Description: There is a 25% reduction in body weight in Pten cKO compared to control littermates
 Body weight measurement
 4 weeks
Object recognition memory1
Decreased
Description: Mice with Pten cKO homozygous MGE derived interneurons ,spend less time exploring the novel object compared to familiar object
 Novel object recognition test
 
Protein phosphorylation1
Increased
Description: There is increased phosphorylated forms of AKT (pAKT) and GSK3 (pFGSK3) in the medial ganglionic eminence (MGE) in mice with Pten cKO MGE interneurons
 Western blot
 E13.5
Mortality/lethality1
 No Change
 
 
Anxiety1
 No change
 Elevated plus maze test; Open field test
 
Cell proliferation1
 No change
 EdU incorporation; phospho-Histone 3 expression; Fluorescence microscopy; Cell counting
 
General locomotor activity1
 No Change
 Open field test
 
Brain size1
 No change
 
 4 weeks
Spontaneous post synaptic event amplitude: inhibitory currents1
 No change
 Whole-cell patch clamp
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Maternal behavior, Repetitive behavior, Seizure, Sensory

PTEN_17_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Older Pten cko males show significant reduction in motor coordination, as they have shorter latency to fall from the accelerating rotarod and also do not improve in performance, unlike wild type controls
Exp Paradigm: Males only
 Accelerating rotarod test
 5-6 months
Cytoskeletal organization: neuronal1
Increased
Description: There is an increase in the neurofilament content in Pten KO Purkinje cell compartments, along with an increase in MAP2 and acetylated alpha-tubulin levels
Exp Paradigm: Males only
 Immunohistochemistry
 
Dendritic spine density and architecture: dendritic tree complexity1
Increased
Description: Pten KO Purkinje cells have thicker dendrites with more focal dendritic swellings and torpedoes compared to wild type mice, that increase with age in Pten cko mice cerebella
Exp Paradigm: Males only
 Immunohistochemistry
 2 months, 4 months, 6 months
Brain cytoarchitecture1
Increased
Description: Size of Pten KO Purkinje cells is increased in all the lobules of the cerebellum by 15% ( 2 months), 50% (4 months) and 60% (9 months)
Exp Paradigm: Males only
 Immunohistochemistry; Cell size measurement
 2 months, 4 months, 9 months
Dendritic spine density and architecture1
Increased
Description: Pten KO Purkinje cells in have hypertrophic spines, notably in the dendrites that are thicker compared to PCs in wild type mice
Exp Paradigm: Males only
 Immunohistochemistry
 2 months, 4 months, 6 months
Neuronal number: Purkinje cells1
Decreased
Description: By 6 months of age there is a significant reduction in Purkinje cell number in the cerebella of Pten cko mice, they have about 50% less PCs than WT
Exp Paradigm: Males only
 Immunohistochemistry
 6 months
Cerebellar morphology: molecular layer thickness1
Increased
Description: Thickness of the molecular layer is increased in the cerebella of the Pten cko mice at 2 and 4 months compared to controls
Exp Paradigm: Males only
 Immunostaining
 2months, 4 months
Action potential firing1
Decreased
Description: Spontaneous as well as evoked action potential firing is decreased in single Pten KO Purkinje cells
Exp Paradigm: Males only
 Cell-attached patch clamp
 3-4.5 months
Presynaptic function: paired-pulse depression (PPD)1
Decreased
Description: Pten KO Purkinje cells had reduced depression (PPD) in the CF- PC synapse
Exp Paradigm: Males only
 Whole-cell patch clamp: short and intermediate inter-stimulus interval
 3-4.5 months
Synaptic transmission: excitatory1
Increased
Description: EPSCs have increased amplitude in the Parallel fiber- Purkinje cell synapse (PF-PC) in Pten cko mice cerebellar slices
Exp Paradigm: Males only
 Cell-attached patch clamp
 3-4.5 months
Apoptosis: brain cells1
Increased
Description: By 9 months of age there is a significant increase in the expression of cleaved caspase-3 in the Purkinje cells indicative of apoptosis, while WT controls have no expression of cleaved caspase three
Exp Paradigm: Males only
 Expression of cleaved caspase-3 (cC3)
 9 months
Synaptic transmission: excitatory1
Increased
Description: EPSCs have increased amplitude in the Climbing fiber- Purkinje cell synapse (CF-PC) in Pten cko mice cerebellar slices
Exp Paradigm: Males only
 Cell-attached patch clamp
 3-4.5 months
Vertical jumping or back flipping1
Increased
Description: Pten cko mice had a significantly increase in jumping or scrabbling behavior compard to wild type controls
Exp Paradigm: Males only
 Observation of repetitive behavior
 3-4months
Self grooming: perseveration1
Decreased
Description: Pten cko mice show decreased time spent in self-grooming compared to wild type controls
Exp Paradigm: Males only
 Grooming behavior assessments
 3-4 months
Social interaction: opposite sex1
Decreased
Description: Pten cko mice spend significantly less time sniffing, allogrooming or mounting a conspecific female compared to wild type control males
Exp Paradigm: Males only
 Reciprocal social interaction test
 3-4months
Social approach1
Decreased
Description: Pten cko mice show no preference to stranger mouse over chamber with an object unlike wild type controls
Exp Paradigm: Males only
 Three-chamber social approach test; Open field test
 3-4months
Signaling1
Increased
Description: Pten cko mice have increased signaling in the mTOR pathway determined by increase in phosphorylated ribosomal protein S6
Exp Paradigm: Males only
 Immunohistochemistry
 4 months
Mortality/lethality1
 No change
 General observations
 Adult
Reproductive function1
 No change
 General observations
 Adult
Cognitive flexibility1
 No change
 Morris water maze test: reversal phase; Water T-maze test: reversal phase
 Adult
Spatial learning1
 No change
 Morris water maze test: hidden platform test
 Adult
Spatial reference memory1
 No change
 Morris water maze test: probe trial
 Adult
General locomotor activity1
 No change
 Three-chamber social approach test; Open field test
 4 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 2-3 months
Cerebellar morphology1
 No change
 Histology
 2-3 months
Presynaptic function: paired-pulse facilitation1
 No change
 Paired-pulse facilitation
 3-4.5 months
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Maternal behavior, Seizure, Sensory


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
AKT1 v-akt murine thymoma viral oncogene homolog 1 207 P31749 IP/WB
Mistafa O , et al. 2010
AMHR2 anti-Mullerian hormone receptor, type II 269 Q16671 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
ANG angiogenin, ribonuclease, RNase A family, 5 283 P03950 Y2H
Stelzl U , et al. 2005
AR androgen receptor 367 P10275 GST; IP/WB
Lin HK , et al. 2004
ARHGAP26 Rho GTPase activating protein 26 23092 Q9UNA1 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
ATF2 activating transcription factor 2 1386 P15336 ChIP
Shen YH , et al. 2006
ATM ataxia telangiectasia mutated 472 Q13315 in vitro kinase assay
Chen JH , et al. 2015
BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) 8314 Q92560 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
Beclin-1 Beclin-1 8678 Q14457 Immunohistochemistry
Ying H , et al. 2015
BMI1 BMI1 polycomb ring finger oncogene 648 P35226 IP/WB
Fan C , et al. 2009
BRAF Serine/threonine-protein kinase B-raf 673 P15056 IP/WB
Silva JM , et al. 2014
C19orf29OS chromosome 19 open reading frame 29 opposite strand 404665 Q8N1I8 Y2H
Sakai Y , et al. 2011
CASP3 caspase 3, apoptosis-related cysteine peptidase 836 P42574 Immunodepletion assay; in vitro proteolysis assay
Torres J , et al. 2003
CASP8 caspase 8, apoptosis-related cysteine peptidase 841 Q14790 Affinity chromatography; MS; IP/WB
Crockett DK , et al. 2005
CAV1 caveolin 1, caveolae protein, 22kDa 857 Q03135 IP/WB
Caselli A , et al. 2002
CAV1 caveolin 1, caveolae protein, 22kDa 857 Q03135 IP/WB
Conde-Perez A , et al. 2015
CBP CREB-binding protein 1387 Q92793 IP/WB
Ding L , et al. 2014
CCNE2 cyclin E2 9134 O96020 Affinity chromatography; MS; IP/WB
Crockett DK , et al. 2005
CDX2 caudal type homeobox 2 1045 Q99626 Immunofluorescence; IP/WB
Liu YQ , et al. 2015
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 ChIP-chip
Subtil-Rodrguez A , et al. 2013
CHGB chromogranin B (secretogranin 1) 1114 P05060 Y2H
Stelzl U , et al. 2005
COPS6 COP9 constitutive photomorphogenic homolog subunit 6 (Arabidopsis) 10980 Q7L5N1 Y2H
Stelzl U , et al. 2005
CREB1 cAMP responsive element binding protein 1 1385 P16220 IP/WB
Duan S , et al. 2015
CREBBP CREB binding protein 1387 Q92793 IP/WB
Duan S , et al. 2015
CRKL v-crk sarcoma virus CT10 oncogene homolog (avian)-like 1399 P46109 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
CSF1 colony stimulating factor 1 (macrophage) 1435 P09603 Luciferase reporter assay
Mandal CC , et al. 2012
CSNK1E casein kinase 1, epsilon 1454 P49674 LUMIER with BACON
Shnitsar I , et al. 2015
CSNK2A1 casein kinase 2, alpha 1 polypeptide 1457 P68400 in vitro kinase assay; GST; IP/WB
Miller SJ , et al. 2002
CSNK2A2 casein kinase 2, alpha prime polypeptide 1459 P19784 in vitro kinase assay; GST; IP/WB
Miller SJ , et al. 2002
CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 1499 Q9WU82 IP/WB
Vogelmann R , et al. 2005
CXXC1 CXXC finger protein 1 30827 Q9P0U4 Y2H; GST
Sakai Y , et al. 2011
DBF4B DBF4 homolog B (S. cerevisiae) 80174 Q8NFT6 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
DJ1 Protein deglycase DJ-1 11315 Q99497 X-ray crystallography
Choi MS , et al. 2014
DLC1 DLC1 Rho GTPase activating protein 10395 Q96QB1 IP/WB
Cao X , et al. 2015
DLG1 discs, large homolog 1 (Drosophila) 1739 Q12959 Y2H; Affinity chromatography
Adey NB , et al. 2000
DLG5 discs, large homolog 5 (Drosophila) 9231 Q8TDM6 LUMIER with BACON
Shnitsar I , et al. 2015
DVL2 dishevelled, dsh homolog 2 (Drosophila) 1856 O14641 LUMIER with BACON; IP/WB; in vitro phosphatase assay
Shnitsar I , et al. 2015
DVL3 dishevelled, dsh homolog 3 (Drosophila) 1857 Q92997 LUMIER with BACON; IP/WB
Shnitsar I , et al. 2015
EEF1A2 eukaryotic translation elongation factor 1 alpha 2 1917 Q05639 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
EGR1 early growth response 1 1958 P18146 Luciferase reporter assay; ChIP; IP/WB; Fluorescence Polarization (FP)
Tell G , et al. 2004
ELAVL1 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R) 1994 Q15717 RNP IP; Protein microarray
Abdelmohsen K , et al. 2009
EML1 echinoderm microtubule associated protein like 1 2009 O00423 Y2H
Sakai Y , et al. 2011
EP300 E1A binding protein p300 2033 Q9Y6B2 IP/WB
Li AG , et al. 2006
EphA2 EPH receptor A2 1969 P29317 X-ray crystallography; IP/WB; in vitro kinase assay; in vitro phosphatase assay; GST
Wei Q , et al. 2014
ESR1 estrogen receptor 1 2099 P03372 GST
Lin HK , et al. 2004
FBN2 fibrillin 2 2201 P35556 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
FLNA filamin A, alpha 2316 P21333 Y2H
Sakai Y , et al. 2011
FRAT1 frequently rearranged in advanced T-cell lymphomas 10023 Q92837 LUMIER with BACON
Shnitsar I , et al. 2015
FRK fyn-related kinase 2444 P42685 IP/WB; in vitro kinase assay
Yim EK , et al. 2009
G3BP2 GTPase activating protein (SH3 domain) binding protein 2 9908 Q9UN86 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
GFRA2 GDNF family receptor alpha 2 2675 E9PD47 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
GLTSCR2 glioma tumor suppressor candidate region gene 2 29997 Q9NZM5 GST; Y2H; IP/WB
Okahara F , et al. 2004
GOPC golgi-associated PDZ and coiled-coil motif containing 57120 Q9HD26 LUMIER with BACON
Shnitsar I , et al. 2015
GPR113 G protein-coupled receptor 113 165082 Q8IZF5 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
GSK3A glycogen synthase kinase 3 alpha 2931 P49840 LUMIER with BACON
Shnitsar I , et al. 2015
GSK3B glycogen synthase kinase 3 beta 2932 P49841 Metabolic labeling with 32P; MS; WB
Al-Khouri AM , et al. 2005
HBA1 hemoglobin, alpha 1 3039 P69905 Y2H
Stelzl U , et al. 2005
HDAC4 histone deacetylase 4 9759 P56524 ChIP; Bimolecular fluorescence complementation assay; IP/WB; Y2H
Reddy SD , et al. 2012
Histone H1.2 Histone H1.2 3006 P16403 MS; FRAP; ChIP; GST; IP/WB; in vitro binding assay ; Immunofluorescence
Chen ZH , et al. 2014
HP1 alpha Chromobox protein homolog 5 23468 P45973 MS; FRAP; ChIP; GST; IP/WB; in vitro binding assay ; Immunofluorescence
Chen ZH , et al. 2014
IKBKB inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta 3551 O14920 LUMIER with BACON
Shnitsar I , et al. 2015
INHBE inhibin, beta E 83729 P58166 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
IRS4 insulin receptor substrate 4 8471 O14654 Affinity chromatography; MS; IP/WB
Crockett DK , et al. 2005
KAT2B K(lysine) acetyltransferase 2B 8850 Q92831 IP/WB; in vitro acetylation assay
Okumura K , et al. 2006
KIF1B kinesin family member 1B 23095 O60333 LUMIER with BACON
Shnitsar I , et al. 2015
KRT14 keratin 14 3861 P02533 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
LEPREL4 leprecan-like 4 10609 Q92791 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
lncRNA-BGL3 beta globin locus transcript 3 (non-protein coding) 103344929 N/A Luciferase reporter assay
Guo G , et al. 2014
MAGI2 membrane associated guanylate kinase, WW and PDZ domain containing 2 9863 Q86UL8 Y2H; GST; IP/WB
Wu X , et al. 2000
MAGI3 membrane associated guanylate kinase, WW and PDZ domain containing 3 260425 Q5TCQ9 Y2H; GST; IP/WB
Wu Y , et al. 2000
MAP2K6 mitogen-activated protein kinase kinase 6 5608 A8K3Y2 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
MAPK14 mitogen-activated protein kinase 14 1432 Q16539 IP/WB
Ittner A , et al. 2012
Mast1 microtubule associated serine/threonine kinase 1 56527 Q9R1L5 GST; Y2H; in vitro kinase assay
Valiente M , et al. 2005
MAST2 microtubule associated serine/threonine kinase 2 23139 Q6P0Q8 Y2H; Affinity chromatography
Adey NB , et al. 2000
MAST3 microtubule associated serine/threonine kinase 3 23031 O60307 GST; Y2H; in vitro kinase assay
Valiente M , et al. 2005
MCRS1 microspherule protein 1 10445 Q96EZ8 IP/WB; GST
Okumura K , et al. 2005
MED12 mediator complex subunit 12 9968 Q93074 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
miR-106b microRNA 106b 406900 N/A Luciferase reporter assay; Immunohistochemistry
Li KK , et al. 2014
miR-130b microRNA 130b 406920 N/A qRT-PCR; IP/WB; Luciferase reporter assay
Yu T , et al. 2015
miR-21 microRNA 21 406991 N/A Luciferase reporter assay; IP/WB
Zhou X , et al. 2014
miR-221 microRNA 221 407006 IP/WB; qRT-PCR
Xie Q , et al. 2014
miR-518c microRNA 518c 574477 N/A Luciferase reporter assay; IP/WB
Tay Y , et al. 2014
miR-638 microRNA 638 693223 N/A Luciferase reporter assay; IP/WB
Tay Y , et al. 2014
miR-7 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 10859 Q8NHL6 Luciferase reporter assay; IP/WB
Wu XN , et al. 2014
miR-802 microRNA 802 768219 N/A ChIP
Li N and Qin ZB 2014
miR-92a microRNA 29a 407021 N/A qRT-PCR
Ke TW , et al. 2014
miR-BART7 ebv-mir-BART7 (MI0003729) N/A N/A Peptide microarray; IP/WB; Luciferase reporter assay
Cai LM , et al. 2014
miR1297 microRNA 1297 100302187 N/A Luciferase reporter assay; IP/WB; MTT assay
Yang NQ , et al. 2014
miR20b microRNA 20b 574032 N/A Luciferase reporter assay; IP/WB
Zhou W , et al. 2014
MIR21 microRNA 21 406991 N/A Luciferase reporter assay
Dey N , et al. 2012
miR214 microRNA 214 406996 N/A Luciferase reporter assay; IP/WB
Zou ZJ , et al. 2014
MIR221 microRNA 221 407006 N/A Luciferase reporter assay
Zhao G , et al. 2013
miR26a microRNA 26a-1 407015 N/A Luciferase reporter assay; IP/WB
Zou ZJ , et al. 2014
MIR29C microRNA 29c 407026 N/A Luciferase reporter assay
Tumaneng K , et al. 2012
MIR374A microRNA 374a 442919 N/A Luciferase reporter assay
Cai J , et al. 2013
miR708 microRNA 708 100126333 N/A Luciferase reporter assay; IP/WB; qRT-PCR
Dileepan M , et al. 2014
MKRN1 makorin ring finger protein 1 23608 Q9UHC7 in vitro ubiquitination assay; In vivo ubiquitination assay
Lee MS , et al. 2015
MME membrane metallo-endopeptidase 4311 P08473 IP/WB; GST
Sumitomo M , et al. 2004
MPP2 membrane protein, palmitoylated 2 (MAGUK p55 subfamily member 2) 4355 Q14168 LUMIER with BACON
Shnitsar I , et al. 2015
MPRIP myosin phosphatase Rho interacting protein 23164 Q6WCQ1 Y2H
Sakai Y , et al. 2011
MTA1 metastasis associated 1 9112 Q13330 ChIP; Luciferase reporter assay; Bimolecular fluorescence complementation assay; IP/WB; Y2H
IP/WB; Immunofluorescence
Reddy SD , et al. 2012
MVP major vault protein 9961 Q14764 IP/WB; Y2H; GST
Yu Z , et al. 2002
NDFIP1 Nedd4 family interacting protein 1 80762 Q9BT67 IP/WB
Mund T and Pelham HR 2010
NDFIP2 Nedd4 family interacting protein 2 54602 B4DGY6 IP/WB
Mund T and Pelham HR 2010
NEDD4 neural precursor cell expressed, developmentally down-regulated 4 4734 P46934 WB; in vitro ubiquitination assay; GST
Wang X , et al. 2008
NKD1 naked cuticle homolog 1 (Drosophila) 85407 Q969G9 LUMIER with BACON
Shnitsar I , et al. 2015
NKD2 naked cuticle homolog 2 (Drosophila) 85409 Q969F2 LUMIER with BACON
Shnitsar I , et al. 2015
PARK7 Parkinson disease (autosomal recessive, early onset) 7 11315 Q99497 IP/WB; GST
Kim YC , et al. 2009
PAX7 paired box 7 5081 P23759 ChIP; qRT-PCR
Duan S , et al. 2015
PDGFRA platelet-derived growth factor receptor, alpha polypeptide 5156 P16234 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
PDGFRB platelet-derived growth factor receptor, beta polypeptide 5159 P09619 WB; Metabolic labeling with 32P; IP/WB; in vitro binding assay; GST
Mahimainathan L and Choudhury GG 2004
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H; GST
Sakai Y , et al. 2011
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 5295 P27986 GST; IP/WB
Ittner A , et al. 2012
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 5295 P27986 IP/WB
Cao X , et al. 2015
PINK1 PTEN induced putative kinase 1 65018 Q9BXM7 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
PKN2 protein kinase N2 5586 Q16513 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
Plk1 polo-like kinase 1 5347 P53350 IP/WB; GST; In vivo ubiquitination assay; LC/MS
Li Z , et al. 2014
PPM1B protein phosphatase, Mg2+/Mn2+ dependent, 1B 5495 O75688 LUMIER with BACON
Shnitsar I , et al. 2015
PPP1CA protein phosphatase 1, catalytic subunit, alpha isozyme 5499 P62136 Antibody Microarray; IP/WB
Flores-Delgado G , et al. 2007
PPP1R10 protein phosphatase 1, regulatory subunit 10 5514 Q96QC0 IP/WB; GST
Kavela S , et al. 2012
PPP2R4 protein phosphatase 2A activator, regulatory subunit 4 5524 Q15257 Affinity chromatography; MS; IP/WB
Crockett DK , et al. 2005
PPP3CA protein phosphatase 3, catalytic subunit, alpha isozyme 5530 Q08209 IP/WB
Mistafa O , et al. 2010
PTK2 PTK2 protein tyrosine kinase 2 5747 Q05397 WB
Tamura M , et al. 1998
PTK2B PTK2B protein tyrosine kinase 2 beta 2185 Q14289 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
PTPN14 protein tyrosine phosphatase, non-receptor type 14 5784 A8K6H6 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
PTPN6 protein tyrosine phosphatase, non-receptor type 6 5777 P29350 IP/WB
Lu Y , et al. 2003
PXN paxillin 5829 P49023 IP/WB
Haier J and Nicolson GL 2002
QRFPR pyroglutamylated RFamide peptide receptor 84109 Q96P65 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
RNF146 ring finger protein 146 81847 Q9NTX7 IP/WB
Li N , et al. 2014
RPL14 ribosomal protein L14 9045 P50914 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 6198 P23443 IP/WB
Liu JL , et al. 2007
RPS6KB2 ribosomal protein S6 kinase, 70kDa, polypeptide 2 6199 Q9UBS0 IP/WB
Liu JL , et al. 2007
RYBP RING1 and YY1 binding protein 23429 Q8N488 Y2H
Sakai Y , et al. 2011
SHARPIN SHANK-associated RH domain interactor 81858 Q9H0F6 IP/WB
He L , et al. 2010
SLC9A3R1 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 9368 O14745 Y2H; Blot overlay assay; GST
Takahashi Y , et al. 2006
SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2 9351 Q6NTG0 Blot overlay assay; GST; IP/WB; Immunodepletion assay
Takahashi Y , et al. 2006
SLUG Zinc finger protein SNAI2 6591 O43623 qRT-PCR; Luciferase reporter assay; IP/WB; ChIP
Uygur B , et al. 2015
SMAD2 SMAD family member 2 4087 Q15796 IP/WB
Hjelmeland AB , et al. 2005
SMAD3 SMAD family member 3 4088 P84022 IP/WB
Hjelmeland AB , et al. 2005
SMTN smoothelin 6525 B4E229 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
SNAI1 snail homolog 1 (Drosophila) 6615 O95863 Luciferase reporter assay; EMSA; ChIP
Escriv M , et al. 2008
SNRPN small nuclear ribonucleoprotein polypeptide N 6638 P63162 LUMIER with BACON
Shnitsar I , et al. 2015
SP1 Sp1 transcription factor 6667 P08047 Luciferase reporter assay; ChIP
Kou XX , et al. 2012
STK11 serine/threonine kinase 11 6794 Q15831 Y2H; IP/WB; in vitro kinase assay
Mehenni H , et al. 2005
STK11 serine/threonine kinase 11 6794 Q15831 LUMIER with BACON
Shnitsar I , et al. 2015
STUB1 STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase 10273 Q9UNE7 IP/WB; GST; in vitro ubiquitination assay
Ahmed SF , et al. 2012
SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) 7341 P63165 in vitro SUMOylation assay; IP/WB
Gonzlez-Santamara J , et al. 2012
SUMO2 SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae) 6613 P61956 in vitro SUMOylation assay; IP/WB
Gonzlez-Santamara J , et al. 2012
TCEB3C transcription elongation factor B polypeptide 3C (elongin A3) 162699 Q8NG57 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
TNKS1 Tankyrase-1 8658 O95271 IP/WB; PARP assay
Li N , et al. 2014
TNKS2 tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase 2 80351 Q9H2K2 IP/WB; PARP assay
Li N , et al. 2014
TP53 tumor protein p53 7157 P04637 IP/WB; EMSA; ChIP
Freeman DJ , et al. 2003
TTBK2 tau tubulin kinase 2 146057 Q6IQ55 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
UBC ubiquitin C 7316 P63279 WB
Wu W , et al. 2003
UBE2I ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast) 7329 P63279 IP/WB
Waite KA and Eng C 2003
UBE2L3 ubiquitin-conjugating enzyme E2L 3 7332 P68036 IP/WB
Waite KA and Eng C 2003
UTP14A UTP14, U3 small nucleolar ribonucleoprotein, homolog A (yeast) 10813 Q9BVJ6 Y2H
Stelzl U , et al. 2005
WNT4 wingless-type MMTV integration site family, member 4 54361 P56705 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
WWP2 WW domain containing E3 ubiquitin protein ligase 2 11060 B4DHF6 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
XIAP X-linked inhibitor of apoptosis 331 P98170 WB; IP/WB; in vitro ubiquitination assay
Van Themsche C , et al. 2009
YAF2 YY1 associated factor 2 10138 Q8IY57 Y2H
Sakai Y , et al. 2011
YY1 YY1 transcription factor 7528 P25490 ChIP; EMSA; Bimolecular fluorescence complementation assay; IP/WB; Y2H
Reddy SD , et al. 2012
ZNF787 zinc finger protein 787 126208 Q6DD87 Affinity chromatography; MS; in silico target prediction
Crockett DK , et al. 2005
Aebp1 AE binding protein 1 11568 Q640N1 IP/WB
Ro HS , et al. 2007
Arx aristaless related homeobox 11878 O35085 ChIP-qPCR
Quill ML , et al. 2011
BMP9 Growth/differentiation factor 2 12165 Q9WV56 Luciferase reporter assay; IP/WB; in vitro phosphatase assay; Immunohistochemistry
Huang J , et al. 2014
Cenpc1 centromere protein C1 12617 P49452 IP/WB
Shen WH , et al. 2007
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
FOXP1 forkhead box P1 108655 P58462 ChIP
Tang B , et al. 2012
Htr2c 5-hydroxytryptamine (serotonin) receptor 2C 15560 P34968 Proximity ligation assay; IP/WB
Kleene R , et al. 2015
Itga3 integrin alpha 3 16400 Q62470 Immunohistochemistry; IP/WB
Yazlovitskaya EM , et al. 2015
Itgb1 Integrin beta-1 16412 P09055 Immunohistochemistry; IP/WB
Yazlovitskaya EM , et al. 2015
Mir17hg Mir17 host gene (non-protein coding) 75957 Luciferase reporter assay
Tung YT , et al. 2015
Mir19a microRNA 19a 723891 Luciferase reporter assay
Zhang L , et al. 2015
Ndfip1 NEDD4 family-interacting protein 1 65113 Q8R0W6 Immunohistochemistry; IP/WB
Howitt J , et al. 2015
Stat3 signal transducer and activator of transcription 3 20848 P42227 ChIP
Zha X , et al. 2011
cyclin D1 G1/S-specific cyclin-D1 595 P24385 IP/WB
Gao L , et al. 2014
Grin2b glutamate receptor, ionotropic, N-methyl D-aspartate 2B 24410 Q00960 IP/WB; in vitro binding assay
Ning K , et al. 2004
Htr2c 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled 25187 P08909 IP/WB
Ji SP , et al. 2006
miR-29a microRNA mir-29a 100314230 N/A qRT-PCR; IP/WB; Luciferase reporter assay; Immunofluorescence
Zou H , et al. 2015
p21 cyclin-dependent kinase inhibitor 1A (p21, Cip1) 1026 P38936 IP/WB
Gao L , et al. 2014
EHMT1 G9a 30971 Q95RU8 ChIP-Seq
Kramer JM , et al. 2011
Cbl N/A 100754737 N/A IP/WB
Rodriguez S and Huynh-Do U 2012
PTPRZ1 N/A 100511294 N/A IP/WB; in vitro phosphatase assay
Shen X , et al. 2012

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