Muscle atrophy in transgenic mice expressing a human TSC1 transgene.
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.
Wan
Min
M
Institute of Developmental Biology and Molecular Medicine, Morgan-Tan International Center for Life Sciences, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
Wu
Xiaohui
X
Guan
Kun-Liang
KL
Han
Min
M
Zhuang
Yuan
Y
Xu
Tian
T
D000818:Animals; D005260:Female; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D011485:Protein Binding; D015398:Signal Transduction; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
D007328:Insulin; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins