
mTOR-related neuropathology in mutant tsc2 zebrafish: …
2017年12月1日 · Phosphorylated ribosomal protein S6 (pS6) is a commonly used marker for mTOR hyperactivation. In this study, immunohistochemical analysis was used to examine the presence of pS6 in the brains of 7 dpf WT, tsc2 +/− and tsc2 −/− larvae.
Gene therapy for tuberous sclerosis complex type 2 in a mouse …
2021年1月8日 · Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - TSC 1 or TSC 2, encoding hamartin and tuberin, respectively. These proteins formed a complex to inhibit mTORC1-mediated cell growth and proliferation. Loss of either protein leads to overgrowth lesions in many vital organs.
Complex Neurological Phenotype in Mutant Mice Lacking Tsc2 in ...
2015年10月22日 · In this study, we generated a novel mutant mouse line (NEX- Tsc2) in which the Tsc2 gene is deleted specifically in postmitotic excitatory neurons of the developing forebrain. Homozygous mutant mice failed to thrive and died prematurely, whereas heterozygous mice appeared normal.
LysM-positive neurons drive Tuberous Sclerosis Complex (TSC) …
2022年12月1日 · In this study, we generated a novel mouse model involving conditional deletion of Tsc1 in lysozyme 2 (Lyz2)-positive cells which replicated several features of brain lesions including epileptic seizures, megalencephaly, highly …
Distinct effects of single amino-acid changes to tuberin on the ...
2004年10月13日 · Approximately 80% of the Tsc2 −/− MEFs expressing exogenous tuberin and approximately 60% of the Tsc1 −/− MEFs expressing exogenous hamartin had no detectable phosphorylated S6 (pS6 ...
Sustained Activation of mTOR Pathway in Embryonic Neural Stem …
2011年11月4日 · Mutant SVZ showed significant reduction in both Tsc1 and Tsc2 proteins, with no activation in pS6 or difference in pERK or pAkt (Figure 5E). Whereas accumulation of Type A neuroblasts could be detected dorsally, alterations in Type B SC distribution were observed along the entire wall of the SVZ ( Figure 5 F).
Inhibition of Growth of TSC2-Null Cells by a PI3K/mTOR Inhibitor …
2019年12月24日 · In this study we demonstrated that rapamycin, at a clinically tolerable concentration (10 nM), inhibited the phosphorylation of S6, but not the critical eIF4E releasing Thr 37/46 phosphorylation sites of 4E-BP1 in TSC2-deficient LAM-derived cells. We also characterized the abundant protein expression of peIF4E within LAM lesions.
Seizure reduction in TSC2-mutant mouse model by an mTOR
(A) pS6 expression in Tsc2 hypomorphic mice (KC+) is three times higher than in CC− littermate controls, indicating a strong mTORC1 upregulation. (B) KC+ mice treated with TC1 (3 mg/kg) show a significant reduction of pS6 levels at 3‐h postadministration.
Seizure reduction in TSC2‐mutant mouse model by an mTOR …
2023年8月6日 · Levels of phosphorylated S6 (pS6) and phosphorylated AKT (pAKT) detected via Western blot in whole brain lysates were compared across Tsc2 hypomorphic genotypes (CC− vs. KC+) and after treatment with either RAD001, TC1, or vehicle as a readout of the mTORC1 and mTORC2 complex activity, respectively. pS6 and pAKT levels, normalized to total ...
Cell-Specific Alterations of Glutamate Receptor Expression in …
Surgically resected human cortical tubers and nondysplastic epileptic cortical samples were analyzed by double-label immunocytochemistry for coexpression of neuronal and glial markers, the TSC1/TSC2 pathway downstream molecule phospho-S6 (pS6) and GluR subunits, and compared with control cortical tissue.