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Publication : Muscle atrophy in transgenic mice expressing a human TSC1 transgene.

First Author  Wan M Year  2006
Journal  FEBS Lett Volume  580
Issue  24 Pages  5621-7
PubMed ID  16996505 Mgi Jnum  J:114651
Mgi Id  MGI:3689665 Doi  10.1016/j.febslet.2006.09.008
Citation  Wan M, et al. (2006) Muscle atrophy in transgenic mice expressing a human TSC1 transgene. FEBS Lett 580(24):5621-7
abstractText  Muscle mass is regulated by a wide range of hormonal and nutritional signals, such as insulin and IGF. Tuberous sclerosis complex (TSC) is an inherited hamartoma disease with tumor growth in numerous organs. TSC is caused by mutation in either TSC1 or TSC2 tumor suppressor genes that negatively regulate insulin-induced S6K activation and cell growth. Here we report that expression of human TSC1 (hTSC1) in mouse skeletal muscle leads to reduction of muscle mass. Expression of hTSC1 stabilizes endogenous TSC2 and leads to inhibition of the mTOR signaling. The hTSC1-mTSC2 hetero-complex and its downstream components remain sensitive to insulin stimulation and nutrition signals. This study suggests that an increase in the steady state level of resident TSC1-TSC2 complex is sufficient to reduce muscle mass and cause atrophy.
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