EXPRESSION OF BOVINE MYF5 INDUCES ECTOPIC SKELETAL-MUSCLE FORMATION IN TRANSGENIC MICE

myf5 is one of a family of four myogenic determination genes that cont rol skeletal muscle differentiation. To study the role of myf5 in vivo , we generated transgenic mice harboring the bovine homolog, bmyf, und er control of the murine sarcoma virus promoter. Ectopic expression of the full-length bmyf transgene was detected in brain and heart tissue samples of F1 progeny from transgenic founder mice. Ectopic bmyf expr ession activated endogenous skeletal myogenic determination genes in t he hearts and brains of transgenic animals. Incomplete skeletal myogen esis in most hearts gave rise to cardiomegaly and focal areas of cardi omyopathy. In brains in which ectopic expression led to a more complet e myogenesis, focal areas of multinucleated, striated myotubes contain ing actin, desmin, and myosin were observed. These unexpected results show that myf5 can initiate myogenic differentiation in vivo, supporti ng the hypothesis that myf5 is responsible for determination of cells to the myogenic lineage in normal embryogenesis.