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Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, genetic association has been found between autism and tuberous sclerosis (and hence the TSC1 and TSC2 genes as well). As well, association with TSC2 and autism has been found in an AGRE cohort (Serajee et al., 2003), and a rare mutation in TSC2 has been identified in an individual with ASD (Oâ??Roak et al., 2012).

Molecular Function

The product of this gene is believed to be a tumor suppressor and is able to stimulate specific GTPases.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism and tuberous sclerosis.
Tuberous sclerosis
ASD
Positive Association
Association of INPP1, PIK3CG, and TSC2 gene variants with autistic disorder: implications for phosphatidylinositol signalling in autism.
ASD
Negative association
Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder.
ASD
Support
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Support
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder.
ASD
ID, epilepsy
Support
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.
Non-syndromic ASD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Highly Cited
Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.
Highly Cited
Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling.
Recent Recommendation
Neuroepileptic correlates of autistic symptomatology in tuberous sclerosis.
Recent recommendation
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Recent Recommendation
Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex.
Recent Recommendation
ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway.
Recent Recommendation
Tuberous sclerosis complex proteins control axon formation.
Recent Recommendation
Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis.
Recent Recommendation
Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN256R001 
  
 N/A 
 N/A 
  
  
  
 GEN256R002 
 missense_variant 
 A to G 
 Met to Val 
 Unknown 
  
 Simplex 
 GEN256R003 
 missense_variant 
 G to A 
 Ala to Thr 
 Unknown 
  
 Simplex 
 GEN256R004 
 missense_variant 
 A to C 
 Lys to Gln 
 Familial 
 Maternal 
 Simplex 
 GEN256R005 
 missense_variant 
 C to T 
 Arg to Cys 
 Unknown 
  
 Simplex 
 GEN256R006 
 missense_variant 
 A to G 
 Ile to Val 
 Unknown 
  
 Simplex 
 GEN256R007 
 missense_variant 
 G to A 
 Ala to Thr 
 Familial (1 case); unknown (1 case) 
 Maternal (1 case) 
 Simplex 
 GEN256R008 
 missense_variant 
 C to G 
 Phe to Leu 
 Unknown 
  
 Simplex 
 GEN256R009 
 missense_variant 
 G to C 
 Glu to Gln 
 Familial 
 Paternal 
 Simplex 
 GEN256R010 
 missense_variant 
 C to T 
 Pro to Leu 
 Unknown 
  
 Simplex 
 GEN256R011 
 missense_variant 
 C to T 
 Ala to Val 
 Familial 
 Paternal 
 Simplex 
 GEN256R012 
 missense_variant 
 G to A 
 Arg to Gln 
 Unknown 
  
 Simplex 
 GEN256R013 
 missense_variant 
 G to A 
 Gly to Arg 
 Unknown 
  
 Simplex 
 GEN256R014 
 missense_variant 
 C to A 
 Ser to Arg 
 Familial 
 Maternal 
 Simplex 
 GEN256R015 
 inframe_deletion 
 delGCTGCCAAG 
 N/A 
 De novo 
  
 Simplex 
 GEN256R016 
 missense_variant 
 C to T 
 Arg1580Trp 
 De novo 
  
 Simplex 
 GEN256R017 
 missense_variant 
 c.433G>A 
 A145T 
  
  
 Multiplex 
 GEN256R018 
 synonymous_variant 
 c.618C>T 
 C206C 
  
  
 Multiplex 
 GEN256R019 
 synonymous_variant 
 c.1143G>A 
 R381R 
  
  
 Multiplex 
 GEN256R020 
 missense_variant 
 c.1292C>T 
 A431V 
  
  
 Multiplex 
 GEN256R021 
 intron_variant 
 c.1839+6G>A 
 Intronic 
  
  
 Multiplex 
 GEN256R022 
 missense_variant 
 c.1912G>A 
 V638M 
  
  
 Multiplex 
 GEN256R023 
 missense_variant 
 c.2155T>C 
 Y719H 
  
  
 Multiplex 
 GEN256R024 
 missense_variant 
 c.2621C>T 
 P874L 
  
  
 Multiplex 
 GEN256R025 
 synonymous_variant 
 c.3126G>T 
 P1042P 
  
  
 Multiplex 
 GEN256R026 
 missense_variant 
 c.3252C>G 
 D1084E 
  
  
 Multiplex 
 GEN256R027 
 missense_variant 
 c.3827C>T 
 S1276F 
  
  
 Multiplex 
 GEN256R028 
 missense_variant 
 c.3914C>T 
 P1305L 
  
  
 Multiplex 
 GEN256R029 
 missense_variant 
 c.3974G>A 
 G1325D 
  
  
 Multiplex 
 GEN256R030 
 missense_variant 
 c.4051G>A 
 E1351K 
  
  
 Multiplex 
 GEN256R031 
 missense_variant 
 c.4316G>A 
 G1439D 
  
  
 Multiplex 
 GEN256R032 
 synonymous_variant 
 c.4341C>T 
  
  
  
 Multiplex 
 GEN256R033 
 missense_variant 
 c.4460C>G 
 S1487C 
  
  
 Multiplex 
 GEN256R034 
 synonymous_variant 
 c.5028G>A 
 L1676L 
  
  
 Multiplex 
 GEN256R035 
 intron_variant 
 c.5069-8C>T 
 Intron 
  
  
 Multiplex 
 GEN256R036 
 synonymous_variant 
 c.5175G>A 
  
  
  
 Multiplex 
 GEN256R037 
 3_prime_UTR_variant 
 c.5429G>A 
 3'UTR 
  
  
 Multiplex 
 GEN256R038 
 3_prime_UTR_variant 
 c.5450G>A 
 3'UTR 
  
  
 Multiplex 
 GEN256R039 
 missense_variant 
  
 I64V 
 Familial 
 Paternal 
 Simplex 
 GEN256R040 
 missense_variant 
  
 H152D 
 Familial 
 Maternal 
 Simplex 
 GEN256R041 
 missense_variant 
  
 K533Q 
 Familial 
 Maternal 
 Simplex 
 GEN256R042 
 missense_variant 
  
 K954R 
 Familial 
 Paternal 
 Simplex 
 GEN256R043 
 missense_variant 
  
 E984Q 
 Familial 
 Paternal 
 Simplex 
 GEN256R044 
 missense_variant 
  
 A1429S 
 Familial 
 Both parents 
 Simplex 
 GEN256R045 
 missense_variant 
 c.2032G>A 
 A678T 
 Unknown 
  
 Unknown 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN256C001 
 intron_variant 
 rs2073636 
 C/T 
 N/A 
 AGRE 
 Discovery 



Model Summary

To provide an alternative model for Tuberous Sclerosis (TSC)

External Links

AllenBrainAtlas   MGI Logo  Entrez Gene

References

Type
Title
Author, Year
Primary
Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.
Additional
Increased levels of anxiety-related behaviors in a Tsc2 dominant negative transgenic mouse model of tuberous sclerosis.
Additional
Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex.
Additional
Loss of Tsc2 in Purkinje cells is associated with autistic-like behavior in a mouse model of tuberous sclerosis complex.
Additional
Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.
Additional
Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex.
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Additional
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.

TSC2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Gene targeted replacement of exon 2 of Tsc2 gene with a neomycin resistance cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: C57BL/6J or BALB/cJ
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Gene targeted replacement of exon 2 of Tsc2 gene with a neomycin resistance cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: 129/SvJae-BALB/cJ or 129/SvJae-C57BL/6J
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_3_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Gene targeted replacement of exon 2 of Tsc2 gene with a neomycin resistance cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: Black Swiss Mice
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_4_DN_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation:
Allele Type: Not Specified
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_5_CN_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Deletion of Tsc2 gene globally
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_6_CN_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Deletion of Tsc2 gene globally
Allele Type: Conditional (Knock Out)
Strain of Origin: Not specified
Genetic Background: 129X1/SvJ and C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_7_CN_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Delection of Tsc2 gene specific to purkinje cells using Pcp2 cre promoter
Allele Type: Conditional (Knock Out)
Strain of Origin: Not specified
Genetic Background: 129X1/SvJ and C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_8_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted deletion of a fragment from codon 74 in exon 2 to codon 164 in exon 5 of Tsc2 gene
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6J
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

TSC2_10_KO_ATG7_DM

Model Type: Genetic
Model Genotype: Double KO (Heterozygous/ Homozygous)
Mutation: Tsc2 heterozygous mice were bred to Atg7 KO mice lacking Atg7 (macroautophagy deficient mice) specifically in the forebrain excitatory neurons to give rise to Tsc2 het an Atg7 neuronal -null double mutants
Allele Type: Targeted (Knock out)
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

TSC2_9_KO_HT_GFP-LC3

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Tsc2 heterozygous mice crossed with GFP-LC3 mice to visualize the autophagosome marker protein LC3
Allele Type: Targeted (Knock out)
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

TSC2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Cardiovascular development and function1
Abnormal
Description: Abnormally inferiorly shifted heart
Exp Paradigm: Histological analysis of embryos
 Histology
 E9-E11.5
General characteristics1
Abnormal
Description: Delayed growth by 1-2 embryonic days; pale skin and edematous gross appearance; pericardial effusions; Exencephaly
Exp Paradigm: General observations
 General observations
 E8-E12.5
General characteristics1
Abnormal
Description: Abnormal general characteristics - hypoplastic liver, poor development of othre abdominal organs, absence of diaphragm, dilated v ascular channels of liver and other abdominal organs
Exp Paradigm: Histological analysis of embryos
 Histology
 E9-E11.5
Mortality/lethality1
Increased
Description: Increased embryonic lethality
Exp Paradigm: General observations
 General observations
 E12.5
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

TSC2_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory - Development of several tumor types: Renal cysts, liver hemangiomas, lung tumors, and angiosarcomas
Exp Paradigm: Histological analysis of embryos
 Histology
 15 months
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory - Renal cysts and adenomas with dense cellular architecture
Exp Paradigm: Histological analysis of kidney
 Histology
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased tuberin expression in cystadenomas
Exp Paradigm: Tuberin Expression
 Immunohistochemistry
 Unreported
Protein expression level evidence1
Increased
Description: Increased gelsolin expression in liver hemangiomas, lung adenomas, and angiosarcomas
Exp Paradigm: Gelsolin Protein Expression
 Immunohistochemistry
 Unreported
Protein expression level evidence1
Increased
Description: Increased gelsolin expression in kidneys
Exp Paradigm: Gelsolin Protein Expression
 Immunohistochemistry
 3, 6, and 12 months
Mortality/lethality1
 No Change
 General observations
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

TSC2_3_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory - Increased frequency of angiosarcomas
Exp Paradigm: Histological Analyses
 Histology
 Unreported
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory - Renal cysts and adenomas greater than 1-10 mm2 size with dense cellular architecture and large solid adenomatous lesions in kidney
Exp Paradigm: Histological analysis of kidney
 Histology
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

TSC2_4_DN_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social interaction1
Decreased
Description: Decreased exploratory activity
Exp Paradigm: Open Field test
 Open field test
 3- 6 months
Anxiety1
Increased
Description: Increased levels of anxiety as demonstrated by significantly less time spent in open arms of elevated plus maze
Exp Paradigm: Elevated plus maze test
 Elevated plus maze test
 3- 6 months
Cued or contextual fear conditioning1
Abnormal
Description: Abnormal contextual discrimination
Exp Paradigm: Cued and Contextual Stimulus (CCS) Assay
 Fear conditioning test: contextual and acoustic cue-dependent
 3- 6 months
Ultrasonic vocalization1
 No Change
 Monitoring ultrasonic vocalizations: maternal separation
 P7
Spatial reference memory1
 No Change
 Morris water maze test
 3- 6 months
Swimming ability1
 No Change
 Morris water maze test
 3- 6 months
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Homeostasis ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

TSC2_5_CN_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain morphology1
Abnormal
Description: Abnormal morphology demonstrated by increased astrocyte number in neocortex and hippocampus
Exp Paradigm: Histological analysis of neocortex and hippocampus
 Histology
 1 week
Brain morphology1
Increased
Description: Increased CA1 pyramidal cell layer width
Exp Paradigm: Histological analysis of hippocampus
 Histology
 3 weeks
Brain morphology1
Abnormal
Description: Abnormal morphology demonstrated by progressive neuronal disorganization in hippocampus with a dispersion of the pyramidal cell layer
Exp Paradigm: Histological analysis of hippocampus
 Histology
 Unreported
Brain size1
Increased
Description: Increased brain weight with generalized megencephaly
 
 3 weeks
Seizures1
Increased
Description: Increased incidence of observable Seizures characterized by head nodding, rearing up on hindlimbs, repetitive forelimb clonus, loss of upright posture
Exp Paradigm: Video-EEG Recordings
 Electroencephalogram (EEG)
 2- 3 weeks
Social interaction2
Decreased
Description: Decreased social novelty indicated by non-significant preference for novel mouse
Exp Paradigm: Male mice: Three chambered apparatus for social novelty
 Three-chamber social approach test
 2 months
Social interaction2
Decreased
Description: Decreased sociaiblity indicated by no preference shown for chamber with stranger mouse or inanimate object
Exp Paradigm: Female mice: Three chambered apparatus for sociability
 Three-chamber social approach test
 2 months
Mortality/lethality1
Increased
Description: Increased lethality related to acute Seizures/status epilepticus or malnutrition/dehydration
Exp Paradigm: General observations
 General observations
 7-10 weeks
Size/growth1
Decreased
Description: Decreased weight gain
Exp Paradigm: General observations
 General observations
 Unreported
Enzyme activity1
Increased
Description: Increased mTOR activation demonstrated by increased phospho-S6 (P-S6) expression
Exp Paradigm: Mtor Activation
 Western blot
 Unreported
Gene expression2
Decreased
Description: Decreased expression of astrocyte glutamate transporter GLT-1
Exp Paradigm: Glt-1 Expression
 Western blot
 Unreported
General characteristics1
 No Change
 General observations
 2 weeks
General characteristics2
 No Change
 General observations
 P30-P31
Mortality/lethality3
 No Change
 General observations
 8-10 weeks
Anxiety2
 No Change
 Open field test
 P47
Enzyme activity4
 No Change
 Western blot
 Unreported
General locomotor activity2
 No Change
 Open field test
 P47
Motor coordination and balance2
 No Change
 Accelerating rotarod test
 2 months
Brain morphology1
 No Change
 Histology
 Unreported
Brain size3
 No Change
 
 4 weeks
Neuronal differentiation and specification in the brain2
 No Change
 Immunohistochemistry: calbindin
 3 months
Stereotypy2
 No Change
 Marble-burying test
 P44
Seizures3
 No Change
 Electroencephalogram (EEG)
 3- 3 weeks
Olfaction2
 No Change
 Buried food test
 P49-54
Vision2
 No Change
 Morris water maze test
 2 months
Social interaction2
 No Change
 Three-chamber social approach test
 2 months
Social interaction2
 No Change
 Three-chamber social approach test
 2 months
 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 ,  

TSC2_6_CN_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General characteristics1
 No Change
 General observations
 P30-P31
Anxiety1
 No Change
 Open field test
 P47
General locomotor activity1
 No Change
 Open field test
 P47
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 2 months
Stereotypy1
 No Change
 Marble-burying test
 P44
Olfaction1
 No Change
 Buried food test
 P49-54
Vision1
 No Change
 Morris water maze test
 2 months
Social interaction1
 No Change
 Three-chamber social approach test
 2 months
Social interaction1
 No Change
 Three-chamber social approach test
 2 months
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,  

TSC2_7_CN_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Gait1
Abnormal
Description: Abnormal wider gait
Exp Paradigm: Inkblot testing
 Footprint analysis
 P61
Motor coordination and balance1
Decreased
Description: Decreased motor coordination demonstrated by shorter latency to fall
Exp Paradigm: Accelerating rotarod test
 Accelerating rotarod test
 5 months
Neuronal differentiation and specification in the brain1
Decreased
Description: Decreased purkinje cell density across folia 2,9, and 10
Exp Paradigm: Calbindin staining across folia 2,9, and 10
 Immunohistochemistry: calbindin
 3 months
Stereotypy1
Increased
Description: Increased repetitive behavior demonstrated by significantly more marbles buried
Exp Paradigm: Male mice: Marble burying assay
 Marble-burying test
 P44
Stereotypy1
Increased
Description: Increased repetitive behavior demonstrated by significantly more marbles buried
Exp Paradigm: Female mice: Marble burying assay
 Marble-burying test
 P44
Social interaction1
Decreased
Description: Decreased sociability indicated by no preference shown for stranger mice
Exp Paradigm: Male mice: Three chambered apparatus for sociability
 Three-chamber social approach test
 2 months
Social interaction1
Decreased
Description: Decreased social novelty indicated by no difference in time spent with novel mouse and familiar mouse
Exp Paradigm: Male mice: Three chambered apparatus for social novelty
 Three-chamber social approach test
 2 months
Social interaction1
Decreased
Description: Decreased sociability indicated by no preference shown for stranger mice
Exp Paradigm: Female mice: Three chambered apparatus for sociability
 Three-chamber social approach test
 2 months
Social interaction1
Decreased
Description: Decreased social novelty indicated by no difference in time spent with novel mouse and familiar mouse
Exp Paradigm: Female mice: Three chambered apparatus for social novelty
 Three-chamber social approach test
 2 months
Anxiety1
Decreased
Description: Decreased anxiety indicated by more time spent in middle of chamber
Exp Paradigm: Male mice: Open field test
 Open field test
 P47
Anxiety1
Increased
Description: Increased anxiety indicated by less time spent in middle
Exp Paradigm: Female mice: Open field test
 Open field test
 P47
General characteristics1
 No Change
 General observations
 P30-P31
Anxiety1
 No Change
 Open field test
 P47
Spatial learning1
 No Change
 Morris water maze test
 P72-77
Spatial reference memory1
 No Change
 Morris water maze test
 P85-89
General locomotor activity1
 No Change
 Open field test
 P47
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 2 months
Olfaction1
 No Change
 Buried food test
 P49-54
Vision1
 No Change
 Morris water maze test
 2 months
Social interaction1
 No Change
 Three-chamber social approach test
 2 months
Social interaction1
 No Change
 Three-chamber social approach test
 2 months
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Homeostasis ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neurophysiology ,   Seizure ,  

TSC2_8_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic spine density and architecture2
Increased
Description: Tsc2 het mice, after 3 weeks of age -the time period of spinal pruning, show increased number of spines in pyramidal neurons of layer V of the auditory cortex and the secondary somatosensory cortex. Compared to wild type (26% reduction in spines) the Tsc2 hets only show a reduction of spines or pruning by 3% ( these numbers are from control mice injected with DMSO)
 Histology: Diolistic labeling
 P29-30
Macroautophagy: neuronal2
Decreased
Description: Tsc2 het mice have reduced macroautophagy in the cortex, due to increase in mTOR activation. Macroautophagy was monitored using the level of protein LC3 known to be associated with autophagosomes.
 Western blot: LC3 protein
 P29
Social memory2
Decreased
Description: Tsc2 het mice had a lower preference index, spend similar amount of time sniffing, the new social target compared to a familiar social target compared to controls.
 Three-chamber social approach test: preference index for new social target compared to familiar social target
 P30-35 (adolescent)
Rearing behavior1
Increased
Description: Increased rearing behavior
Exp Paradigm: Social interaction test
 Reciprocal social interaction test
 3-7 months
Social approach2
Decreased
Description: Tsc2 het mice had a lower preference index towards the social target compared to a non social target compared to controls. Tsc2 do spend more type with the social target compared to non social target, but the preference index is smaller than controls
 Three-chamber social approach test: preference index for social target versus non social target
 P30-35 (adolescent)
Social interaction1
Decreased
Description: Decreased social interaction demonstrated by shorter time engaged in active exploration i.e. exploring a novel mouse
Exp Paradigm: Social interaction test with novel mouse scored for sniffing, allo-grooming, mounting, and following
 Reciprocal social interaction test
 3-7 months
Rearing behavior1
Increased
Description: Increased rearing behavior
Exp Paradigm: Social interaction test with novel mouse scored for rearing
 Reciprocal social interaction test
 3-7 months
Social interaction1
Decreased
Description: Decreased active interaction
Exp Paradigm: Social interaction test
 Reciprocal social interaction test
 3-7 months
Social interaction2
Decreased
Description: Tsc2 het mice spend less time sniffing the new stimulus mouse compared to wild type controls
 Reciprocal social interaction test
 P30-35 (adolescent)
Depression1
Increased
Description: Increased depression indicated by longer immobility time
Exp Paradigm: Tail suspension test
 Tail suspension test
 3-7 months
Object recognition memory2
Decreased
Description: Tsc2 het mice spend less time with new object compared to wild type littermate controls
 Novel object recognition test
 P30-35 (adolescent)
Enzyme activity1
Increased
Description: Increased mTOR activation demonstrated by increased phospho-S6K levels
Exp Paradigm: Mtor Activation
 Western blot
 Unreported
Gene expression1
Increased
Description: Increased expression of Tsc1, Gsk3b, Mapk1, Deptor, and Ulk1 mRNA
Exp Paradigm: Gene Expression
 Quantitative PCR (qRT-PCR)
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased tuberin expression
Exp Paradigm: Tuberin Expression
 Western blot
 Unreported
Protein expression level evidence2
Increased
Description: Tsc2 het mice show increased expression of presynaptic marker synaptophysin
 Immunostaining: synaptophysin
 P30-35 (adolescent)
Gene expression1
Decreased
Description: Decreased mRNA expression of Tsc2
Exp Paradigm: Mrna Expression Intensity
 Gene expression microarray
 Unreported
Gene expression1
Increased
Description: Increased mRNA expression of Tsc1, Gsk3b, Mapk1, Ulk1, Igbp1, Rps6, Deptor, and Eef2k
Exp Paradigm: Mrna Expression Intensity
 Gene expression microarray
 Unreported
Protein expression level evidence2
Increased
Description: Tsc2 het mice show increased expression of post synaptic marker PSD95
 Immunostaining: PSD95
 P30-35 (adolescent)
Protein phosphorylation1
Decreased
Description: Decreased Akt phosphorylation with No Change in total Akt levels
Exp Paradigm: Akt Phosphorylation
 Western blot
 Unreported
General characteristics1
 No Change
 General observations
 3-7 months
Size/growth1
 No Change
 General observations
 3-7 months
Anxiety1
 No Change
 Light-dark exploration test
 3-7 months
Anxiety2
 No Change
 Open field test
 P30-35 (adolescent)
Exploratory activity1
 No Change
 Home cage behavior: novel object interaction
 3-7 months
Protein expression level evidence1
 No Change
 Western blot
 Unreported
General locomotor activity1
 No Change
 Open field test
 8-10 weeks
General locomotor activity: Ambulatory activity2
 No Change
 Open field test: time spent at center, distance traveled, rearing
 P30-35 (adolescent)
Grip strength1
 No Change
 Vertical pole test
 8-10 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 8-10 weeks
Dendritic spine density and architecture2
 No Change
 Histology: Diolistic labeling
 P19-30
Dendritic spine density and architecture: dendritic tree complexity2
 No Change
 Histology: Diolistic labeling
 P19-20 and P30
Self grooming: perseveration2
 No Change
 Grooming behavior assessments: test cage after habituation
 P30-35 (adolescent)
Olfaction1
 No Change
 Buried food test
 3-7 months
Pain or nociception1
 No Change
 Tail flick test
 3-7 months
Social dominance1
 No Change
 Tube test of social dominance
 3-7 months
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,  

TSC2_10_KO_ATG7_DM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic spine density and architecture1
Increased
Description: By P29 the double knock out mice for Tsc2 (het) Atg (null) show increased number of spines as a result of lack of spinal pruning that reduces the number of spines by 26% in wild type mice between P20 and P28. In the double knock out there is only a reduction by 2%
 Histology: Diolistic labeling
 P29
Social memory1
Decreased
Description: The double knock out Tsc2 het/ Atg null mice show impaired social preference in the three chamber test, towards the new social target compared to the familiar social target
 Three-chamber social approach test: social novelty
 Unreported
Social approach1
Decreased
Description: The double knock out Tsc2 het/ Atg null mice show impaired social preference or sociability in the three chamber test, towards the social target compared to the non social target
 Three-chamber social approach test: sociability or social preference
 Unreported
Dendritic spine density and architecture1
 No Change
 Histology: Diolistic labeling
 P20
 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 ,  

TSC2_9_KO_HT_GFP-LC3

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Macroautophagy: neuronal1
Decreased
Description: Tsc2 het mice with GFP tagged LC3 protein show reduced levels of the labeled LC3 puncta confirming a reductionin autophagosome formation and macroautophagy in the cortical pyramidal neurons
 Immunostaining: GFP-LC3 in brain
 Unreported
Protein expression level evidence1
Increased
Description: Tsc2 het mice with GFP tagged LC3 protein have increased levels of phospho S6, indicating increased mTOR activation, in cortical pyramidal neurons
 Western blot: pS6 in cortex
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
4-Sep septin 4 5414 O43236 Y2H
Sakai Y 2011
ACTN2 actinin, alpha 2 88 P35609 Y2H
Sakai Y 2011
AKT1 v-akt murine thymoma viral oncogene homolog 1 207 P31749 Metabolic labeling with 32P; IP/WB
Dan HC 2002
ANKRD35 ankyrin repeat domain 35 148741 Q8N283 Y2H
Sakai Y 2011
AR androgen receptor 367 P10275 ChIP-Seq; Capillary gel electrophoresis (CGE)
Rajan P 2011
axin1 axin 1 734298 Q9YGY0 IP/WB
Mak BC 2003
CALM1 calmodulin 1 (phosphorylase kinase, delta) 801 P62158 Phage display; GST; Bimolecular fluorescence complementation assay
Noonan DJ 2002
CAV1 caveolin 1, caveolae protein, 22kDa 857 Q03135 IP/WB
Yamamoto Y 2002
CCNA2 cyclin A2 890 P20248 IP/WB
Catania MG 2001
CCNB1 cyclin B1 891 P14635 IP/WB
Catania MG 2001
CCND1 cyclin D1 595 P24385 IP/WB
Zacharek SJ 2005
CCND2 cyclin D2 894 P30279 IP/WB
Zacharek SJ 2005
CCND3 cyclin D3 896 P30281 IP/WB
Zacharek SJ 2005
CDK1 cyclin-dependent kinase 1 983 P06493 IP/WB
Catania MG 2001
CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) 1027 P46527 IP/WB
Rosner M 2004
CRB3 crumbs homolog 3 (Drosophila) 92359 Q9BUF7 IP/WB; GST
Massey-Harroche D 2007
CUL4A cullin 4A 8451 Q13619 IP/WB
Hu J 2008
DAPK1 death-associated protein kinase 1 1612 P53355 Solid phase binding assay; IP/WB; Metabolic labeling with 32P; WB
Stevens C 2009
DDB1 damage-specific DNA binding protein 1, 127kDa 1642 Q16531 IP/WB
Hu J 2008
DDIT4 DNA-damage-inducible transcript 4 54541 Q9NX09 IP/WB
Vega-Rubin-de-Celis S 2010
EEF1A1 eukaryotic translation elongation factor 1 alpha 1 1915 P68104 Y2H
Sakai Y 2011
ESR1 estrogen receptor 1 2099 P03372 IP/WB; GST
York B 2005
FBXW5 F-box and WD repeat domain containing 5 54661 Q969U6 Y2H; WB; in vitro ubiquitination assay; IP/WB
Hu J 2008
GAPDH glyceraldehyde-3-phosphate dehydrogenase 2597 P04406 Y2H
Sakai Y 2011
GRB2 growth factor receptor-bound protein 2 2885 P62993 Y2H
Wang J 2008
GSK3B glycogen synthase kinase 3 beta 2932 P49841 IP/WB
Mak BC 2003
HERC1 hect (homologous to the E6-AP (UBE3A) carboxyl terminus) domain and RCC1 (CHC1)-like domain (RLD) 1 8925 Q15751 IP; MS; IP/WB
Chong-Kopera H 2006
HSPA1A heat shock 70kDa protein 1A 3303 P08107 IP; MS; IP/WB
Nellist M 2005
HTRA1 HtrA serine peptidase 1 5654 Q92743 Y2H; GST; IP/WB; in vitro proteolysis assay
Campioni M 2010
INADL InaD-like (Drosophila) 10207 Q8NI35 Y2H; GST; IP/WB
Massey-Harroche D 2007
LNX1 ligand of numb-protein X 1, E3 ubiquitin protein ligase 84708 Q8TBB1 Y2H; in vitro ubiquitination assay; IP/WB
Guo Z 2012
MAPK1 mitogen-activated protein kinase 1 5594 P28482 IP/WB; Metabolic labeling with 32P; IP; MS
Ma L 2005
MAPKAP1 mitogen-activated protein kinase associated protein 1 79109 Q9BPZ7 IP/WB
Huang J 2009
MKRN1 makorin ring finger protein 1 23608 Q9UHC7 Y2H
Sakai Y 2011
MLST8 MTOR associated protein, LST8 homolog (S. cerevisiae) 64223 Q9BVC4 IP/WB
Huang J 2009
MRPL21 mitochondrial ribosomal protein L21 219927 Q7Z2W9 Y2H
Sakai Y 2011
MTOR mechanistic target of rapamycin (serine/threonine kinase) 2475 P42345 IP/WB
Huang J 2009
MYCBP2 MYC binding protein 2 23077 O75592 Y2H; GST; IP/WB
Murthy V 2004
NAA10 N(alpha)-acetyltransferase 10, NatA catalytic subunit 8260 A6NM98 GST; IP/WB; in vitro acetylation assay
Kuo HP 2010
NEK1 NIMA (never in mitosis gene a)-related kinase 1 4750 Q96PY6 Y2H
Surpili MJ 2003
PHLDB1 pleckstrin homology-like domain, family B, member 1 23187 Q86UU1 Y2H
Sakai Y 2011
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H; GST
Sakai Y 2011
PIN1 peptidylprolyl cis/trans isomerase, NIMA-interacting 1 5300 Q13526 Y2H
Vinayagam A 2011
PKD1 polycystic kidney disease 1 (autosomal dominant) 5310 P98161 IP/WB
Dere R 2010
PLK1 polo-like kinase 1 5347 P53350 IP/WB
Astrinidis A 2006
RAB5A RAB5A, member RAS oncogene family 5868 P20339 IP/WB
Yamamoto Y 2002
RALA v-ral simian leukemia viral oncogene homolog A (ras related) 5898 P11233 IP/WB
Castro AF 2003
RAP1A RAP1A, member of RAS oncogene family 5906 P62834 IP/WB
Yamamoto Y 2002
RB1CC1 RB1-inducible coiled-coil 1 9821 Q8TDY2 IP/WB
Gan B 2005
RHEB Ras homolog enriched in brain 6009 Q15382 GTP hydrolysis assay
Garami A 2003
RICTOR RPTOR independent companion of MTOR, complex 2 253260 Q6R327 IP/WB
Huang J 2009
RPL4 ribosomal protein L4 6124 P36578 Y2H
Sakai Y 2011
RPS6KA1 ribosomal protein S6 kinase, 90kDa, polypeptide 1 6195 Q15418 Metabolic labeling with 32P; in vitro kinase assay; IP/WB
Roux PP 2004
RPSA ribosomal protein SA 3921 P08865 Y2H
Sakai Y 2011
SERPINI1 serpin peptidase inhibitor, clade I (neuroserpin), member 1 5274 Q99574 Y2H; IP/WB
Sakai Y 2011
SIRT1 sirtuin 1 23411 A8K128 IP/WB
Ghosh HS 2010
SLC13A3 solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3 64849 Q8WWT9 Y2H
Sakai Y 2011
SRCRB4D scavenger receptor cysteine rich domain containing, group B (4 domains) 136853 Q8WTU2 Y2H
Sakai Y 2011
TACC3 transforming, acidic coiled-coil containing protein 3 10460 Q9Y6A5 Y2H; GST; IP/WB
Gómez-Baldó L 2010
TBC1D7 TBC1 domain family, member 7 51256 Q9P0N9 IP/WB; GST
Nakashima A 2007
TFAP4 transcription factor AP-4 (activating enhancer binding protein 4) 7023 Q01664 IP/WB; EMSA
Habib SL 2010
TK1 thymidine kinase 1, soluble 7083 P04183 Y2H
Vinayagam A 2011
TSC1 tuberous sclerosis 1 7248 Q92574 Y2H; IP/WB
van Slegtenhorst M 1998
TSC2 tuberous sclerosis 2 7249 P49815 IP/WB
Hoogeveen-Westerveld M 2012
UBC ubiquitin C 7316 P63279 IP/WB
Zheng L 2008
UBE3A ubiquitin protein ligase E3A 7337 Q05086 IP/WB; WB; GST
Zheng L 2008
US3 N/A 2703401 B9VQJ7 IP/WB; in vitro kinase assay
Chuluunbaatar U 2010
USPL1 ubiquitin specific peptidase like 1 10208 Q5W0Q7 Y2H
Sakai Y 2011
YWHAB tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide 7529 P31946 GST
Nellist M 2002
YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 7531 P62258 GST
Nellist M 2002
YWHAG tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide 7532 P61981 GST
Nellist M 2002
YWHAH tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide 7533 Q04917 GST
Nellist M 2002
YWHAQ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide 10971 P27348 GST
Nellist M 2002
YWHAZ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide 7534 P63104 Y2H; GST; IP/WB
Nellist M 2002
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC 2011
NGFRAP1 nerve growth factor receptor (TNFRSF16) associated protein 1 27018 Q00994 IP/WB
Yasui S 2007
PIP4ks Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma 117150 Q91XU3 IP/WB;in vitro kinase assay;LC-MS/MS
Mackey AM 2014
Ppp2ca protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform 19052 P63330 IP; MS; IP/WB
Lee WJ 2007
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM 2014
Foxo1 forkhead box O1 56458 Q9R1E0 Y2H; IP/WB; GST
Cao Y 2006
Mapkapk2 MAP kinase-activated protein kinase 2 17164 P49138 in vitro kinase assay
Li Y 2003
PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit 5562 Q13131 EMSA; Metabolic labeling with 32P; in vitro kinase assay; 2-D phosphopeptide mapping
Inoki K 2003
PTK2 PTK2 protein tyrosine kinase 2 5747 Q05397 IP/WB; GST; WB
Gan B 2006
RABEP1 rabaptin, RAB GTPase binding effector protein 1 9135 Q15276 Y2H
Xiao GH 1997
ROCK1 Rho-associated, coiled-coil containing protein kinase 1 6093 Q13464 IP/WB; in vitro kinase assay
Park JH 2011
Sfn stratifin 55948 O70456 GST; IP/WB
Liu MY 2002
SMAD2 SMAD family member 2 4087 Q15796 IP/WB; GST
Birchenall-Roberts MC 2004
SMAD3 SMAD family member 3 4088 P84022 IP/WB; GST
Birchenall-Roberts MC 2004
Spry2 sprouty homolog 2 (Drosophila) 306141 Q5HZA2 IP/WB
Scott CL 2010
ATPsynd ATP synthase subunit d, mitochondrial 42291 Q24251 Peptide microarray;IP/WB
Sun X 2014

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