MYOD IS REQUIRED FOR MYOGENIC STEM-CELL FUNCTION IN ADULT SKELETAL-MUSCLE

To investigate the function of MyoD in adult skeletal muscle, we inter bred MyoD mutant mice with mdx mice, a model for Duchenne and Becker m uscular dystrophy. Mice lacking both MyoD and dystrophin displayed a m arked increase in severity of myopathy leading to premature death, sug gesting a role for MyoD in muscle regeneration. Examination of MyoD mu tant muscle revealed elevated numbers of myogenic cells; however, myob lasts derived from these cells displayed normal differentiation potent ial in vitro. Following injury, MyoD mutant muscle was severely defici ent in regenerative ability, and we observed a striking reduction in t he in vivo proliferation of myogenic cells during regeneration. Theref ore, we propose that the failure of MyoD-deficient muscle to regenerat e efficiently is not caused by a reduction in numbers of satellite cel ls, the stem cells of adult skeletal muscle, but results from an incre ased propensity for stem-cell self-renewal rather than progression thr ough the myogenic program.