Grb10 regulates the development of fiber ... - The FASEB Journal

The FASEB Journal • Research Communication

Grb10 regulates the development of fiber number in skeletal muscle Lowenna J. Holt,*,1 Nigel Turner,*,§ Nancy Mokbel,* Sophie Trefely,* Timo Kanzleiter,* Warren Kaplan,† Christopher J. Ormandy,‡,§ Roger J. Daly,‡,§,2 and Gregory J. Cooney*,§,2 *Diabetes and Obesity Research Program, †Peter Wills Bioinformatics Centre, and ‡Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; and §St. Vincent’s Hospital Clinical School, University of New South Wales, Sydney, New South Wales, Australia Grb10 is an intracellular adaptor protein that acts as a negative regulator of insulin and insulinlike growth factor 1 (IGF1) receptors. Since global deletion of Grb10 in mice causes hypermuscularity, we have characterized the skeletal muscle physiology underlying this phenotype. Compared to wild-type (WT) controls, adult mice deficient in Grb10 have elevated body mass and muscle mass throughout adulthood, up to 12 mo of age. The muscle enlargement is not due to increased myofiber size, but rather an increase in myofiber number (142% of WT, P