ACTIVATION OF THE MYOGENIN PROMOTER DURING MOUSE EMBRYOGENESIS IN THEABSENCE OF POSITIVE AUTOREGULATION

Myogenin, a member of the MyoD family of helix-loop-helix proteins, ca n induce myogenesis in a wide range of cell types. In addition to acti vating muscle structural genes, members of the MyoD family can autoact ivate their own and cross-activate one another's expression in transfe cted cells. This has led to the hypothesis that autoregulatory loops a mong these factors provide a mechanism for amplifying and maintaining the muscle-specific gene expression program in vivo. Here, we make use of myogenin-null mice to directly test this hypothesis, To investigat e whether the myogenin protein autoregulates the myogenin gene during embryogenesis, we introduced a myogenin-lacZ transgene into mice harbo ring a null mutation at the myogenin locus. Despite a severe deficienc y of skeletal muscle in myogenin-null neonates, the myogenin-lacZ tran sgene was expressed normally in myogenic cells throughout embryogenesi s. These results show that myogenin is not required for regulation of the myogenin gene and argue against the existence of a myogenin autore gulatory loop in the embryo.