JAX
Mouse Strain Datasheet - 005680
STOCK Tsc1tm1Djk/J
Also Known As: Tsc1 flox, Tsc1c
These floxed mutant mice possess loxP sites flanking exons 17 and 18 of the Tsc1 gene. This mutant strain may be useful in tissue-specific studies including tuberous sclerosis or other hamartoma syndromes, regulation of the actin cytoskeleton and motility, cellular and organismal glucose homeostasis, cell growth responses, apoptosis regulation, and regulation of cell size.
Donating Investigator
David J. Kwiatkowski, Brigham and Women's Hospital
Genetic overview
| Genetic Background | Generation |
|---|---|
|
F?+pN1F12
|
Tsc1tm1Djk
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Conditional ready (e.g. floxed), No functional change) | Tsc1 | tuberous sclerosis 1 |
Detailed Description
Homozygous mice are viable, fertile, normal in size, have normal expression of hamartin (the targeted gene's protein product), have no growth or behavioral defects, and are devoid of tumors through age 18 months. This mutant carries a "floxed" allele of the endogenous gene. When combined with a mutant carrying a Cre recombinase gene under the control of a promoter of interest, exons 17 and 18 of Tsc1 are deleted in the tissue of interest. This mutant may be useful in many tissue-specific studies including tuberous sclerosis or other hamartoma syndromes, regulation of the actin cytoskeleton and motility, cellular and organismal glucose homeostasis, cell growth responses, apoptosis regulation, and regulation of cell size.
When bred to a strain expressing Cre recombinase in neuronal cells (see Stock No. 003966 for example), this mutant mouse strain may be useful in studies of tuberous sclerosis.
When bred to a strain expressing Cre recombinase in oocytes of the primordial follicles (see Stock No. 011062 for example), this mutant mouse strain may be useful in studies of primordial follicle quiescence and activation.
When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of hepatic lipid metabolism.
Importation of this model was supported by the Tuberous Sclerosis Alliance.
Development
A targeting vector containing a loxP-flanked neomycin resistance-thymidine kinase gene cassette preceding exon 17 and a third loxP site downstream of exon 18 was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were backcrossed for germ-line transmission to C57BL/6J, BALB/cJ, or 129/SvJae mice. The resulting heterozygotes were intercrossed to produce homozygotes on a mixed background.
Control Suggestions
Selected References
- Kwiatkowski DJ; Zhang H; Bandura JL; Heiberger KM; Glogauer M; el-Hashemite N; Onda H. 2002. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 11(5):525-34. PubMed: 11875047MGI: J:75243
Tsc1tm1Djk
Allele Symbol: Tsc1tm1Djk
| Allele Name | targeted mutation 1, David J Kwiatkowski |
|---|---|
| Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
| Allele Synonym(s) | Tsc1L; Tsc1c; Tsc1fl; Tsc1flox; Tsc1lox |
| Gene Symbol and Name | Tsc1, tuberous sclerosis 1 |
| Gene Synonym(s) | LAM; TSC; hamartin |
| Strain of Origin | 129S4/SvJae |
| Chromosome | 2 |
| General Note | Phenotypic Similarity to Human Syndrome: Angiosarcoma/Lymphangiosarcoma J: 231316. |
| Molecular Note | 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. |
| Mutations Made By | David Kwiatkowski, Brigham and Women's Hospital |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Research Tools
- Cancer Research
- Hamartoma Syndromes
- Cre-lox System
- loxP-flanked Sequences
- Cancer Research
Mammalian Phenotype Terms by Genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Tsc1tm1Djk/Tsc1tm1Djk
involves: 129S4/SvJae * C57BL/6
liver/biliary system phenotype
- abnormal hepatocyte morphology
- increase in hepatocyte size following adenoviral cre retro-orbital injection (MGI Ref ID J:167208)
- abnormal liver physiology
- cre injected mice are unable to generate ketones when given sodium octanoate (MGI Ref ID J:167208)
- decrease in liver protein content following adenoviral cre retro-orbital injection (MGI Ref ID J:167208)
- in cre injected mice, the liver is largely refractory to fast induced shrinkage (MGI Ref ID J:167208)
- enlarged liver
- about a 40% increase in liver mass following adenoviral cre retro-orbital injection (MGI Ref ID J:167208)
homeostasis/metabolism phenotype
- decreased body temperature
- in fasted cre injected mice (MGI Ref ID J:167208)
- decreased circulating ketone body level
- markedly lower serum ketones in young fasted cre injected mice but not in aged fasted cre injected mice (MGI Ref ID J:167208)
behavior/neurological phenotype
- hypoactivity
- in fasted cre injected mice (MGI Ref ID J:167208)
Genotype: Tsc1tm1Djk/Tsc1tm1Djk
involves: 129S4/SvJae
neoplasm
- neoplasm
- mice do not develop mesothelioma following injection of adenovirus expressing Cre into the bladder or intraperitoneally at 2-3 months of age (MGI Ref ID J:212578)
The following phenotype relates to a compound genotype created using this strain
Genotype: Tsc1tm1Djk/Tsc1+ Tg(Pcp2-cre)2Mpin/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/cJ * C57BL/6J
behavior/neurological phenotype
- abnormal response to novel odor
- abnormal sexual interaction
- mice show impaired male-female social interactions, with reductions in the time that mice spend interacting compared to controls (MGI Ref ID J:186699)
- abnormal social investigation
- in a 3-chambered assay of social approach and preference for social novelty, mice exhibit social impairments, showing no differences between the time spend in the chamber or in interaction with the novel mouse versus the novel object unlike controls (MGI Ref ID J:186699)
- in a social novelty paradigm, mice show no preference for social novelty (MGI Ref ID J:186699)
- excessive vocalization
- P5-P12 pups show increased vocalizations (MGI Ref ID J:186699)
- increased grooming behavior
- increase in self-grooming rates (MGI Ref ID J:186699)
nervous system phenotype
- abnormal Purkinje cell dendrite morphology
- increase in spine density on Purkinje cell dendrites (MGI Ref ID J:186699)
- abnormal nervous system physiology
- Purkinje cell excitability is reduced, with Purkinje cells showing lower, graded spontaneous spiking rate, and current injection evokes fewer action potentials in Purkinje cells (MGI Ref ID J:186699)
- despite receiving normal functioning synaptic inputs, the output of the cerebellar cortex is reduced, both tonically and in response to incoming excitatory drive (MGI Ref ID J:186699)
- injection of small hyperpolarizing currents results in smaller voltage changes in Purkinje cells, indicating a decrease in the effective input resistance (MGI Ref ID J:186699)
Genotype: Tsc1tm1Djk/Tsc1tm1.1Djk Tg(Syn1-cre)671Jxm/0
involves: 129S4/SvJae * C57BL/6 * CBA
mortality/aging
- premature death
- discontinuation of drug treatment at P30 results in clinical symptom improvement for 1-2 weeks followed by clinical deterioration and death at 79 days for rapamycin-treated and 77 days for RAD001-treated mutants (MGI Ref ID J:136366)
- median survival of 35 days, with no survivors beyond 65 days (MGI Ref ID J:121858)
- mice treated with rapamycin or RAD001 (mTOR inhibitor) show 90-100% survival to 80 days of age compared to median survival of 33 days for untreated mutants (MGI Ref ID J:136366)
growth/size/body region phenotype
- slow postnatal weight gain
- after P5 until death, mutants fail to gain weight at same rate as controls; average maximum weight is 10 grams (MGI Ref ID J:121858)
nervous system phenotype
- abnormal brain morphology
- abnormal brain wave pattern
- interictal (seizure) 1-2 second bursts of high-amplitude 7-8 hertz spikes are observed with high frequency compared with controls; these are without obvious clinical correlate (MGI Ref ID J:121858)
- mice aged P21-48 display 3 types of electrographic abnormalities: short spike bursts observed in all mice examined, occasionally spontaneous period of desynchronization with electrodecrement and at low incidence, frequent high-amplitude sharp waves (MGI Ref ID J:121858)
- abnormal cerebral cortex morphology
- laminar organization is less distinct than in the 6 cortical layers of controls (MGI Ref ID J:121858)
- mild cortical disorganization is observed in mutants with or without rapamycin treatment (MGI Ref ID J:136366)
- mutants display subset of enlarged pS6-positive cells at base of cortex and in cortical layer V; drug treatment results in marked reduction in size of enlarged cells (MGI Ref ID J:136366)
- unusually large cells are observed in all six layers in mutants, particularly in layer V; layer of enlarged cells is seen at gray-white matter border throughout cerebral cortex at P21 (MGI Ref ID J:121858)
- abnormal dendrite morphology
- in hippocampal neuron cultures, neuronal dendritic spine density is reduced >20% compared to controls (MGI Ref ID J:136366)
- with rapamycin treatment, spine density is marginally increased; spine length however is increased 9% compared to treated and untreated controls or untreated mutants (MGI Ref ID J:136366)
- abnormal dentate gyrus morphology
- enlarged cells are observed in hilus (MGI Ref ID J:121858)
- abnormal hippocampus pyramidal cell layer
- enlarged cells are seen throughout pyramidal cell layer, particularly in CA3 region (MGI Ref ID J:121858)
- abnormal hippocampus region morphology
- enlarged ectopic cells are seen outside the CA1-CA3 fields in stratum oriens and stratum radiatum (MGI Ref ID J:121858)
- abnormal myelination
- hypomyelination is observed in brains of mutants (MGI Ref ID J:121858)
- myelination particularly in cortex is impaired due to decreased myelin production by oligodendrocytes; rapamycin treatment works to restore myelination throughout brain with greatest improvement in cortex and hippocampus (MGI Ref ID J:136366)
- oligodendrocyte number and distribution appears similar to wild-type (MGI Ref ID J:121858)
- abnormal neocortex morphology
- contains some enlarged cells (MGI Ref ID J:121858)
- abnormal neuron differentiation
- abnormal neuron morphology
- Nissl bodies and filamentous aggregates are often detected in enlarged neurons, prominently in brainstem but rarely in enlarged cortical cells (MGI Ref ID J:121858)
- in somatosensory cortex, layer V neurons often have major dendrites extending tangentially and diagonally to the pia, in contrast to control neurons which mainly have long apical dendrite oriented directly toward pial surface; rapamycin treatment initiated at P7 does not significantly decrease abnormally oriented dendrite percentaged at P7 does not significantly decrease abnormally oriented dendrite percentage (MGI Ref ID J:136366)
- many pyramidal neurons demonstrate dysplastic features including increased size and thicker dendritic arbors compared to control neurons (MGI Ref ID J:121858)
- population of neurons in lateral somatosensory cortex are considerably enlarged compared with those in controls; size is significantly reduced after drug treatment (from 1.8-fold to 1.2-fold), but effect reverses when treatment is stopped (MGI Ref ID J:136366)
- some neurons are aberrantly localized outside primary pyramidal cell layers; ectopic neurons are isolated, not organized into clusters or columns (MGI Ref ID J:121858)
- some neurons in somatosensory cortex show 60% increase in soma size relative to controls (MGI Ref ID J:121858)
- increased brain weight
- brain weight to body weight ratio is significantly greater (2.4-fold) in mutants compared to wild-type; with rapamycin/RAD001 treatment, difference from control is significantly reduced but still observed (MGI Ref ID J:136366)
- seizures
- after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death (MGI Ref ID J:121858)
- mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe (MGI Ref ID J:121858)
- severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds (MGI Ref ID J:121858)
- sporadic seizures
- only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso (MGI Ref ID J:121858)
behavior/neurological phenotype
- abnormal involuntary movement
- clasping behavior and tremor are significantly ameliorated by rapamycin/RAD001 treatment relative to untreated animals at 30, 60, and 100 days postnatal (MGI Ref ID J:136366)
- abnormal limb posture
- at death, usually in third to fifth postnatal week, mice are found with extensor posture of fore- and hindlimbs (MGI Ref ID J:121858)
- hunched posture
- develops by by third or fourth postnatal week (MGI Ref ID J:121858)
- hyperactivity
- apparent by P10 (MGI Ref ID J:121858)
- hypoactivity
- mice show progressive decline in activity with limited mobility by third or fourth postnatal week (MGI Ref ID J:121858)
- increased startle reflex
- apparent by P10 (MGI Ref ID J:121858)
- limb grasping
- display posterior limb-clasping behavior when lifted by tail (MGI Ref ID J:121858)
- seizures
- after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death (MGI Ref ID J:121858)
- mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe (MGI Ref ID J:121858)
- severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds (MGI Ref ID J:121858)
- sporadic seizures
- only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso (MGI Ref ID J:121858)
- straub tail
- tail dorsiflexion is exhibited (MGI Ref ID J:121858)
- tremors
- progressive high-frequency trunk and limb tremor apparent by P10 (MGI Ref ID J:121858)
skeleton phenotype
- abnormal spine curvature
- kyphosis is significantly improved in rapamycin/RAD001-treated mice compared with untreated mutants (MGI Ref ID J:136366)
cellular phenotype
Genotype: Tsc1tm1Djk/Tsc1tm1Djk Tg(Alb-cre)21Mgn/0
involves: 129S4/SvJae * C57BL/6 * DBA
homeostasis/metabolism phenotype
- abnormal homeostasis
- gene expression analysis indicates that fat utilization and glucose production are promoted in mutants (MGI Ref ID J:171445)
- decreased circulating triglyceride level
- impaired glucose tolerance
- mutants exhibit mild but significant glucose intolerance (MGI Ref ID J:171445)
- insulin resistance
- however, fasting plasma glucose and insulin levels are normal (MGI Ref ID J:171445)
- insulin levels at 30 minutes following glucose administration are higher in mutants than controls, indicating insulin resistance (MGI Ref ID J:171445)
- mutants exhibit a slight reduction in systemic insulin sensitivity (MGI Ref ID J:171445)
liver/biliary system phenotype
- abnormal hepatocyte morphology
- increase in hepatocyte cell size (MGI Ref ID J:171445)
- abnormal hepatocyte physiology
- hepatocytes are resistant to steatosis induced by a high-fat diet (MGI Ref ID J:171445)
- enlarged liver
- mutants develop hepatomegaly (MGI Ref ID J:171445)
- liver/biliary system phenotype
- mutants normally do not exhibit hepatic steatosis, however when fed a high-fat diet and treated with rapamycin, they develop steatosis and show increased levels of hepatic triglycerides (MGI Ref ID J:171445)
Genotype: Tsc1tm1Djk/Tsc1tm1Djk Tg(Gdf9-icre)5092Coo/?
involves: 129S4/SvJae * C57BL/6J
endocrine/exocrine gland phenotype
- abnormal ovarian follicle morphology
- injection with rapamycin reverses the overactivation of primordial follicles, indicative that mTORC1 activity is responsible for increased activation of follicles (MGI Ref ID J:155357)
- mutants exhibit premature activation of the entire primordial follicle pool by P23, leading to follicle depletion and premature ovarian failure in early adulthood (2-3 months of age) (MGI Ref ID J:155357)
homeostasis/metabolism phenotype
- increased circulating follicle stimulating hormone level
- higher levels at 3-4 months of age (MGI Ref ID J:155357)
- increased circulating luteinizing hormone level
- higher levels at 3-4 months of age (MGI Ref ID J:155357)
reproductive system phenotype
- abnormal ovarian follicle morphology
- injection with rapamycin reverses the overactivation of primordial follicles, indicative that mTORC1 activity is responsible for increased activation of follicles (MGI Ref ID J:155357)
- mutants exhibit premature activation of the entire primordial follicle pool by P23, leading to follicle depletion and premature ovarian failure in early adulthood (2-3 months of age) (MGI Ref ID J:155357)
- reduced female fertility
- from 6-27 weeks of age, females produce at most 2 litters of normal size and then become infertile after around 12-13 weeks (MGI Ref ID J:155357)
Genotype: Tsc1tm1Djk/Tsc1tm1Djk Tg(Pcp2-cre)2Mpin/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/cJ * C57BL/6J
behavior/neurological phenotype
- abnormal learning/memory/conditioning
- mice exhibit similar acquisition learning of a submerged escape-platform location compared to controls, however when the escape platform location is reversed, mutants show impaired learning of the new platform location (MGI Ref ID J:186699)
- rapamycin treatment prevents the reversal learning impairment (MGI Ref ID J:186699)
- abnormal response to novel odor
- abnormal sexual interaction
- mice show impaired male-female social interactions, with reductions in the time that mice spend interacting compared to controls (MGI Ref ID J:186699)
- abnormal social investigation
- in a 3-chambered assay of social approach and preference for social novelty, mice show social impairments, showing no differences between the time spend in the chamber or in interaction with the novel mouse versus the novel object (MGI Ref ID J:186699)
- in a social novelty paradigm, mice show no preference for social novelty (MGI Ref ID J:186699)
- treatment with rapamycin results in normal social behavior (MGI Ref ID J:186699)
- ataxia
- excessive vocalization
- P5-P12 pups show increased vocalizations (MGI Ref ID J:186699)
- impaired coordination
- increased grooming behavior
- increase in self-grooming rates (MGI Ref ID J:186699)
- short stride length
- (MGI Ref ID J:186699)
nervous system phenotype
- abnormal Purkinje cell dendrite morphology
- increase in spine density on Purkinje cell dendrites (MGI Ref ID J:186699)
- abnormal Purkinje cell morphology
- Purkinje cell soma area is increased at 4 weeks of age (MGI Ref ID J:186699)
- Purkinje cells display abnormal axonal projections with numerous protrusions and abnormal collateralization (MGI Ref ID J:186699)
- markers for endoplasmic reticulum and oxidative stress are elevated indicating elevated neuronal stress of Purkinje cells (MGI Ref ID J:186699)
- abnormal cerebellar Purkinje cell layer
- abnormal nervous system physiology
- Purkinje cell excitability is reduced, with Purkinje cells showing lower, graded spontaneous spiking rate, and current injection evokes fewer action potentials in Purkinje cells (MGI Ref ID J:186699)
- despite receiving normal functioning synaptic inputs, the output of the cerebellar cortex is reduced, both tonically and in response to incoming excitatory drive (MGI Ref ID J:186699)
- however, alterations in synaptic transmission are not apparent in mutants (MGI Ref ID J:186699)
- injection of small hyperpolarizing currents results in smaller voltage changes in Purkinje cells, indicating a decrease in the effective input resistance (MGI Ref ID J:186699)
Genotype: Tsc1tm1Djk/Tsc1tm1Djk Tg(Syn1-cre)671Jxm/0
involves: 129S4/SvJae * C57BL/6 * CBA
mortality/aging
- premature death
- clinical features, survival, and brain pathology are stated to be identical to that of Tsc1tm1DjkTsc1tm1.1DjkTg(Syn1-cre)671Jxm conditional mutants; however no data are presentedTg(Syn1-cre)671Jxm conditional mutants; however no data are presented (MGI Ref ID J:121858)
growth/size/body region phenotype
- abnormal body size
- (MGI Ref ID J:121858)
nervous system phenotype
- abnormal nervous system morphology
- (MGI Ref ID J:121858)
- abnormal nervous system physiology
- (MGI Ref ID J:121858)
behavior/neurological phenotype
- abnormal behavior
- (MGI Ref ID J:121858)
References
- Kwiatkowski DJ; Zhang H; Bandura JL; Heiberger KM; Glogauer M; el-Hashemite N; Onda H. 2002. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 11(5):525-34. PubMed: 11875047MGI: J:75243
Additional - Tsc1tm1Djk related
- Adhikari D; Zheng W; Shen Y; Gorre N; Hamalainen T; Cooney AJ; Huhtaniemi I; Lan ZJ; Liu K. 2009. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet :. PubMed: 19843540MGI: J:155357
- Ai D; Baez JM; Jiang H; Conlon DM; Hernandez-Ono A; Frank-Kamenetsky M; Milstein S; Fitzgerald K; Murphy AJ; Woo CW; Strong A; Ginsberg HN; Tabas I; Rader DJ; Tall AR. 2012. Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice. J Clin Invest 122(5):1677-87. PubMed: 22466652MGI: J:184540
- Ai D; Chen C; Han S; Ganda A; Murphy AJ; Haeusler R; Thorp E; Accili D; Horton JD; Tall AR. 2012. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest 122(4):1262-70. PubMed: 22426206MGI: J:184553
- Anderl S; Freeland M; Kwiatkowski DJ; Goto J. 2011. Therapeutic value of prenatal rapamycin treatment in a mouse brain model of tuberous sclerosis complex. Hum Mol Genet 20(23):4597-604. PubMed: 21890496MGI: J:234598
- Armour EA; Carson RP; Ess KC. 2012. Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules. Am J Physiol Renal Physiol 303(4):F584-92. PubMed: 22674026MGI: J:188431
- Banerjee S; Crouse NR; Emnett RJ; Gianino SM; Gutmann DH. 2011. Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner. Proc Natl Acad Sci U S A 108(38):15996-6001. PubMed: 21896734MGI: J:176586
- Barilari M; Bonfils G; Treins C; Koka V; De Villeneuve D; Fabrega S; Pende M. 2017. ZRF1 is a novel S6 kinase substrate that drives the senescence programme. EMBO J 36(6):736-750. PubMed: 28242756MGI: J:241874
- Bateup HS; Johnson CA; Denefrio CL; Saulnier JL; Kornacker K; Sabatini BL. 2013. Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron 78(3):510-22. PubMed: 23664616MGI: J:197979
- Beirowski B; Wong KM; Babetto E; Milbrandt J. 2017. mTORC1 promotes proliferation of immature Schwann cells and myelin growth of differentiated Schwann cells. Proc Natl Acad Sci U S A 114(21):E4261-E4270. PubMed: 28484008MGI: J:242200
- Benhamron S; Pattanayak SP; Berger M; Tirosh B. 2015. mTOR activation promotes plasma cell differentiation and bypasses XBP-1 for immunoglobulin secretion. Mol Cell Biol 35(1):153-66. PubMed: 25332234MGI: J:224314
- Benhamron S; Tirosh B. 2011. Direct activation of mTOR in B lymphocytes confers impairment in B-cell maturation andloss of marginal zone B cells. Eur J Immunol 41(8):2390-6. PubMed: 21674478MGI: J:176815
- Byles V; Covarrubias AJ; Ben-Sahra I; Lamming DW; Sabatini DM; Manning BD; Horng T. 2013. The TSC-mTOR pathway regulates macrophage polarization. Nat Commun 4:2834. PubMed: 24280772MGI: J:206148
- Carson RP; Van Nielen DL; Winzenburger PA; Ess KC. 2012. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis 45(1):369-80. PubMed: 21907282MGI: J:179842
- Castets P; Lin S; Rion N; Di Fulvio S; Romanino K; Guridi M; Frank S; Tintignac LA; Sinnreich M; Ruegg MA. 2013. Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy. Cell Metab 17(5):731-44. PubMed: 23602450MGI: J:198962
- Chang JW; Zhang W; Yeh HS; de Jong EP; Jun S; Kim KH; Bae SS; Beckman K; Hwang TH; Kim KS; Kim DH; Griffin TJ; Kuang R; Yong J. 2015. mRNA 3'-UTR shortening is a molecular signature of mTORC1 activation. Nat Commun 6:7218. PubMed: 26074333MGI: J:223030
- Chen C; Liu Y; Liu R; Ikenoue T; Guan KL; Liu Y; Zheng P. 2008. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 205(10):2397-408. PubMed: 18809716MGI: J:140099
- Chen H; Zhang L; Zhang H; Xiao Y; Shao L; Li H; Yin H; Wang R; Liu G; Corley D; Yang Z; Zhao Y. 2013. Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+ CD25+ Foxp3+ regulatory T-cell development in mice. FASEB J 27(10):3979-90. PubMed: 23882125MGI: J:203700
- Chevere-Torres I; Kaphzan H; Bhattacharya A; Kang A; Maki JM; Gambello MJ; Arbiser JL; Santini E; Klann E. 2012. Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the DeltaRG mouse model of tuberous sclerosis complex. Neurobiol Dis 45(3):1101-10. PubMed: 22198573MGI: J:182345
- Ci X; Kuraoka M; Wang H; Carico Z; Hopper K; Shin J; Deng X; Qiu Y; Unniraman S; Kelsoe G; Zhong XP. 2015. TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation. PLoS One 10(5):e0127527. PubMed: 26000908MGI: J:235410
- Cornu M; Oppliger W; Albert V; Robitaille AM; Trapani F; Quagliata L; Fuhrer T; Sauer U; Terracciano L; Hall MN. 2014. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21. Proc Natl Acad Sci U S A 111(32):11592-9. PubMed: 25082895MGI: J:213931
- Daikoku T; Terakawa J; Hossain MM; Yoshie M; Cappelletti M; Yang P; Ellenson LH; Dey SK. 2014. Mammalian target of rapamycin complex 1 and cyclooxygenase 2 pathways cooperatively exacerbate endometrial cancer. Am J Pathol 184(9):2390-402. PubMed: 25058027MGI: J:213943
- Daikoku T; Yoshie M; Xie H; Sun X; Cha J; Ellenson LH; Dey SK. 2013. Conditional deletion of Tsc1 in the female reproductive tract impedes normal oviductal and uterine function by enhancing mTORC1 signaling in mice. Mol Hum Reprod 19(7):463-72. PubMed: 23475984MGI: J:211231
- Damsky W; Micevic G; Meeth K; Muthusamy V; Curley DP; Santhanakrishnan M; Erdelyi I; Platt JT; Huang L; Theodosakis N; Zaidi MR; Tighe S; Davies MA; Dankort D; McMahon M; Merlino G; Bardeesy N; Bosenberg M. 2015. mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation. Cancer Cell 27(1):41-56. PubMed: 25584893MGI: J:218894
- Dasgupta B; Yi Y; Hegedus B; Weber JD; Gutmann DH. 2005. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Res 65(21):9843-50. PubMed: 16267007MGI: J:102692
- Di Nardo A; Kramvis I; Cho N; Sadowski A; Meikle L; Kwiatkowski DJ; Sahin M. 2009. Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner. J Neurosci 29(18):5926-37. PubMed: 19420259MGI: J:148479
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