This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, genetic association exists between autism and tuberous sclerosis (and hence the TSC1 and TSC2 genes as well).
Molecular Function
This gene encodes a growth inhibitory protein thought to play a role in the stabilization of tuberin and has been implicated as a tumor supressor.
Tsc1 mutant mice showed behavioral changes, such as decreased social approach and novelty and increased grooming and behavioral inflexibility. Activation of RCrusI rescued impaired social approach and novelty behaviors but had no effect on increased grooming or perseveration.
References
Type
Title
Author, Year
Primary
A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeted disruption of exons 17 and 18 of Tsc1 gene using homologous recombination leading to termination of translation.
Allele Type: Targeted (Knock Out)
Strain of Origin: 129/Sv
Genetic Background: C57BL/6J, BALB/cJ; 129/SvJae
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted disruption of exons 17 and 18 of Tsc1 gene using homologous recombination leading to termination of translation.
Allele Type: Targeted (Knock Out)
Strain of Origin: 129/Sv
Genetic Background: C57BL/6J, BALB/cJ; 129/SvJae
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17-18 of the Tsc1 gene using GFAP1-cre, in astrocytes/glia
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17 and 18 of Tsc1 gene using Dlx5/6 enhancer -cre expressed, in interneurons
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57/SV129
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional heterozygous deletion of exons 17 and 18 of Tsc1 gene using L7 cre from Purkinje neurons of the cerebellum
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17 and 18 of Tsc1 gene using L7 cre from Purkinje neurons of the cerebellum
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional heterozygous deletion of exons 17 and 18 of Tsc1 gene using Emx-cre, in the neurons and glia of the neocortex, hippocampus and pallium starting E10.5
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exons 17 and 18 of Tsc1 gene using Emx-cre, in the neurons and glia of the neocortex, hippocampus and pallium, E10.5
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted disruption of exons 6-8 replaced by IRES-EGFP-pA expression unit resulting in frameshift.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17 and 18 of Tsc1 gene using Gbx2-creER, in thalamic cells with tamoxifen administration on E12.5. Thalamic projections were labeled using R26tdTomato
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17 and 18 of Tsc1 gene using Gbx2-creER, in thalamic cells with tamoxifen administration on E18.5.Thalamic projections were labeled using R26tdTomato
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17-18 of the Tsc1 gene using CamkII-cre, resulting in the gradual loss of Tsc1 from neurons, glia in the deep cortical layers at the time period during which spinal pruning is believed to take place ( between P20:P29-30)
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: C57BL/6 * 129SvJae
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 17-18 of the Tsc1 gene using L7-cre in Purkinje cells of the cerebellum
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: C57BL/6J * 129SvJae * BALB/cJ
ES Cell Line: Mutant ES Cell Line: Model Source: Jackson Laboratories
Model Type:
Genetic
Model Genotype:
Wildtype
Mutation:
Seven-week-old wildtype C57BL/6 male mice were injected with Tsc1-siRNA (1441941, NM_022887.2), bilaterally in the dorsal striatum using a stereotaxic apparatus, resulting in a reduction of Tsc1 transcript levels to 0.4 fold compared with control siRNA injected mice.
Allele Type: Knockdown
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: Daehan BioLink (Eumsung, Chungbuk, Republic of Korea)
Model Type:
Genetic LOF
Model Genotype:
Homozygous
Mutation:
Tsc1 conditional-ready floxed mice were crossed to pv-cre mice. in the conditional-ready mice, a floxed neo-tk cassette was inserted into the intron preceding exon 17 and a third loxp site was introduced downstream of exon 18 by homologous recombination. to confirm the time course and specificity of cre expression in pv-cre mice were crossed with rce^gfp reporter mice. (pv-cre; tsc1flox/flox mice)
Allele Type: Conditional knockout
Strain of Origin: 129S4/SvJae
Genetic Background: Not reoprted
ES Cell Line: NA
Mutant ES Cell Line: J1 (ES Cell)
Model Source: 11875047; Jackson Laboratories (Cat# 005680)
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Tsc1 conditional-ready floxed mice were crossed to pv-cre mice. in the conditional-ready mice, a floxed neo-tk cassette was inserted into the intron preceding exon 17 and a third loxp site was introduced downstream of exon 18 by homologous recombination. to confirm the time course and specificity of cre expression in pv-cre mice were crossed with rce^gfp reporter mice. (pv-cre; tsc1flox/+ mice)
Allele Type: Conditional knockout
Strain of Origin: 129S4/SvJae
Genetic Background: Not reoprted
ES Cell Line: NA
Mutant ES Cell Line: J1 (ES Cell)
Model Source: 11875047; Jackson Laboratories (Cat# 005680)
Model Type:
Genetic LOF
Model Genotype:
Homozygous
Mutation:
Tsc1 conditional-ready floxed mice were crossed to nkx2.1-cre mice. in the conditional-ready mice, a floxed neo-tk cassette was inserted into the intron preceding exon 17 and a third loxp site was introduced downstream of exon 18 by homologous recombination. to confirm the time course and specificity of cre expression in nkx2.1-cre mice were crossed with rce^gfp reporter mice. (nkx2.1-cre; tsc1flox/flox mice). nkx2.1 is a transcription factor expressed at e10.5 by gabaergic cell precursors in the medial ganglionic eminence (mge), which gives rise to cortical pv- and somatostatin-expressing (sst) gabaergic cells.
Allele Type: Conditional knockout
Strain of Origin: 129S4/SvJae
Genetic Background: Not reoprted
ES Cell Line: NA
Mutant ES Cell Line: J1 (ES Cell)
Model Source: 11875047; Jackson Laboratories (Cat# 005680)
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Tsc1 conditional-ready floxed mice were crossed to nkx2.1-cre mice. in the conditional-ready mice, a floxed neo-tk cassette was inserted into the intron preceding exon 17 and a third loxp site was introduced downstream of exon 18 by homologous recombination. to confirm the time course and specificity of cre expression in pv-cre mice were crossed with rce^gfp reporter mice. (nkx2.1-cre; tsc1flox/+ mice). nkx2.1 is a transcription factor expressed at e10.5 by gabaergic cell precursors in the medial ganglionic eminence (mge), which gives rise to cortical pv- and somatostatin-expressing (sst) gabaergic cells.
Allele Type: Conditional knockout
Strain of Origin: 129S4/SvJae
Genetic Background: Not reoprted
ES Cell Line: NA
Mutant ES Cell Line: J1 (ES Cell)
Model Source: 11875047; Jackson Laboratories (Cat# 005680)
Description: Mildly retarded brain development assessed by neuroepithelial cell proliferation and organziation with a visible developmental delay
Exp Paradigm: Immunohistochemical analysis
Description: Delayed development; pale skin; increased edema with pericardial effusion; hypoplastic liver with abnormal growth of abdominal organs
Exp Paradigm: General observation; histological analysis- histology
Description: Delayed development; pale skin; increased edema with pericardial effusion; hypoplastic liver with abnormal growth of abdominal organs
Exp Paradigm: General observation; histological analysis-general observations
Description: Increased size and presence of lesions consisting of vascular channels of highly variable size which consisted of cuboidal-columnar endothelial cells and smooth muscle cells
Exp Paradigm: Histological analysis
Description: Abnormal development of multiple bilateral renal cystadenomas with progression to renal cell carcinoma
Exp Paradigm: Histological analysis
Description: Abnormal morphology demonstrated by increased astrocyte number in neocortex and hippocampus
Exp Paradigm: Histological analysis of neocortex and hippocampus
Description: Increased area of gabaergic neurons and increased cell size in cerebral cortex and hippocampus
Exp Paradigm: Cell counting and size analyses of coronal brain sections
Description: Decreased number of gaba-positive neurons within rostral and parietal regions of neocortex and dentate gyrus of hippocampus
Exp Paradigm: Cell counting and size analyses of coronal brain sections
Description: Abnormal cytoarchitecture indicated by large p86 positive cells in isolation or cluters within neocortical layer i
Exp Paradigm: Cell counting and size analyses of coronal brain sections
Description: Increased latency to clonic-forebrain seizures with continued flurothyl expsoure
Exp Paradigm: Synchronized video-electroencephalography (eeg) monitoring after treatment with flurothyl, a volatile chemoconvulsant
Description: Decreased latency to onset of seizure induction with flurothyl
Exp Paradigm: Synchronized video-electroencephalography (eeg) monitoring after treatment with flurothyl, a volatile chemoconvulsant
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in latency to fall from the rotarod compared with controls.
Exp Paradigm: NA
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in distance travelled on the open field compared with controls.
Exp Paradigm: NA
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in distance travelled in the elevated plus maze compared with controls.
Exp Paradigm: NA
Description: Mutant mice with tsc1 deleted in purkinje cells show increase in volumes of crusi, crusii and decrease in volumes of lateral nucleus, medial nucleus, interposed nucleus, anterior lobule, compared with controls.
Exp Paradigm: NA
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in spontaneous firing frequency in purkinje cells compared with controls.
Exp Paradigm: NA
Description: Decreased social novelty indicated by no significant preference for novel over familiar animal
Exp Paradigm: Three chambered assay for social interaction with a novel mouse and a familiar mouse
Description: Decreased social interaction demonstrated by no difference in time spent with novel mouse vs. object
Exp Paradigm: Three chambered assay for social interaction with a novel mouse and an object
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in time spent investigating social odorants compared with controls.
Exp Paradigm: NA
Description: Decreased male-female social interaction demonstrated by reduction in time spent interaction
Exp Paradigm: Open field male female interaction paradigm
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in time spent in the center of the open field compared with controls.
Exp Paradigm: NA
Description: Mutant mice with tsc1 deleted in purkinje cells show decrease in ability to locate the platform when it was switched to the opposite quadrant compared with controls.
Exp Paradigm: NA
Description: Decreased social interaction demonstrated by no difference in time spent with novel mouse vs. object
Exp Paradigm: Three chambered assay for social interaction with a novel mouse and an object
Description: Het mice with tsc1 deleted in purkinje cells show decrease in time spent investigating social odorants compared with controls.
Exp Paradigm: NA
Description: Het mice with tsc1 deleted in purkinje cells show decrease in time spent in the center of the open field compared with controls.
Exp Paradigm: NA
Description: L7-tsc1 hets have significantly reduced learning of the cr in eyeblink conditioning accompanied by a significantly reduced response amplitude. the latter represents the neural representation of the learned response of eye blinking.
Exp Paradigm: Males only
Description: Het mice with tsc1 deleted in purkinje cells show decrease in ability to locate the platform when it was switched to the opposite quadrant compared with controls.
Exp Paradigm: NA
Description: Increased neuronal stress indicated by elevated levels of er (grp78) and oxidative (ho1) stress in pcs
Exp Paradigm: Immunohistochemical analysis with antibodies for grp78 and ho1
Description: Decreased cognitive flexibility demonstrated by impaired learning of new platform location
Exp Paradigm: Reversal learning paradigm using a water t-maze test
Description: Increased neuronal stress indicated by elevated levels of er (grp78) and oxidative (ho1) stress in pcs
Exp Paradigm: Immunohistochemical analysis with antibodies for grp78 and ho1
Description: Decreased social novelty indicated by no significant preference for novel over familiar animal
Exp Paradigm: Three chambered assay for social interaction with a novel mouse and a familiar mouse
Description: Decreased cognitive flexibility demonstrated by impaired learning of new platform location
Exp Paradigm: Reversal learning paradigm using a water t-maze test
Description: Tsc1 mutant mice exhibited a decrease in the amount of time spent interacting with a wildtype mate of the same sex compared to wildtype controls.
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
Description: Tsc1 mutant mice exhibited impaired social memory compared to control mice, spending comparable amounts of time exploring the novel versus familiar (non-cagemate) mouse, whereas wildtype mice spent significantly more time exploring the novel mouse.
Exp Paradigm: Novel mouse: stranger (S2); Familiar mouse: non-cagemate previously introduced for 10 mins (S1).
Description: Increased geometric mean soma rea of ps6+ neurons
Exp Paradigm: Immunohistochemical analysis using somatodendritic marker microtubule-associated protein 2 (map2)
Description: Abnormal thalamocortical circuit development indicated by diffuse pattern of cortical innervation: individual barrels were indistinguishable in layer iv and overabundant projections in deep layers of thalamic ventrobasal nuclear complex to vibrissa barrels in layer iv of primary somatosensory cortex
Exp Paradigm: Immunohistochemical analysis using r26tdtomato to label thalamic projections
Description: Abnormal neural activity indicated by higher power across multiple frequencies, especially 3 hz range
Exp Paradigm: Local field potentials in vibrissal representation of primary si
Description: Abnormal firing properties demonstrated by constant amplitude of action potential during tonic firing and mean spiking frequency during burst firing
Exp Paradigm: NA
Description: Increased spontaneous seizures with highly stereotyped behavior, followed by loss of upright posture, then a tonic-clonic state with convulsive, twisted posture
Exp Paradigm: General observations
Description: Abnormal neural activity indicated by higher power across multiple frequencies, especially 3 hz range
Exp Paradigm: Local field potentials in vibrissal representation of primary si
Description: At p29-30, after the spinal pruning stage and when most deep cortical neurons lack tsc1 in the tsc1 cn ko mice, the density of spine is increased in the pyramidal neurons of layer v auditory and secondary somatosensory cortices
Exp Paradigm: NA
Functional magnetic resonance imaging: connectivity1
Abnormal
Description: Tsc1 mutant mice showed significant changes in structural connectivity between bilateral crusi and multiple contralateral cortical areas compared to controls. tsc1 mutant mice showed significant increase in structural connectivity between rcrusi white matter and parietal association areas compared to controls. tsc1 mutant mice show abnormal asymmetric structural connectivity between the right and left crusi and contralateral cerebral cortices, compared to controls.
Exp Paradigm: NA
Description: Tsc1 mutant mice showed increased behavioral inflexibility compared to controls, measured by reduced performance in the reversal learning task.
Exp Paradigm: NA
Description: Tsc1-sirna injected mice show no preference for a social stimulus over an empty cage compared with controls and spend less time interacting with the social target compared with controls.
Exp Paradigm: NA
Description: Tsc1-sirna injected mice show decrease in time spent with an unfamiliar object over a familiar object compared with controls.
Exp Paradigm: NA
Description: Tsc1-sirna injected mice show decrease in tsc1 transcript in the dorsal striatum, 2 days after injection.
Exp Paradigm: Striatal tissue was used for qrt pcr.
Description: At p45 a higher proportion of pv cells co-localized with ps6 and showed a 2.5-fold increase in ps6 intensity in pv cell somata indicating cortical pv cells show increased mtor activity
Description: At p45 a higher proportion of pv cells co-localized with ps6 and showed a 2.5-fold increase in ps6 intensity in pv cell somata indicating cortical pv cells show increased mtor activity
Description: Increased activation of ampk, as indicated by the expression levels of phospho-ampk (at t172) and a trend towards increased levels of pulk1
