MYOD OR MYF-5 IS REQUIRED FOR THE FORMATION OF SKELETAL-MUSCLE

Mice carrying null mutations in the myogenic regulatory factors Myf-5 or MyoD have apparently normal skeletal muscle. To address whether the se two factors functionally substitute for one another in myogenesis, mice carrying mutant Myf-5 and MyoD genes were interbred. While mice l acking both MyoD and Myf-5 were born alive, they were immobile and die d soon after birth. Northern blot and S1 nuclease analyses indicated t hat Myf-5(-/-);MyoD(-/-) mice expressed no detectable skeletal muscle- specific mRNAs. Histological examination of these mice revealed a comp lete absence of skeletal muscle. Immunohistochemical analysis indicate d an absence of desmin-expressing myoblast-like cells. These observati ons suggest that either Myf-5 or MyoD is required for the determinatio n of skeletal myoblasts, their propagation, or both during embryonic d evelopment and indicate that these factors play, at least in part, fun ctionally redundant roles in myogenesis.