Muscle atrophy in transgenic mice expressing a human TSC1 transgene.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wan, M; Wu, X; Guan, K-L; Han, M; Zhuang, Y; Xu, T

Published Date

  • October 16, 2006

Published In

Volume / Issue

  • 580 / 24

Start / End Page

  • 5621 - 5627

PubMed ID

  • 16996505

Pubmed Central ID

  • 16996505

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2006.09.008

Language

  • eng

Conference Location

  • England