FUNCTIONAL REDUNDANCY OF THE MUSCLE-SPECIFIC TRANSCRIPTION FACTORS MYF5 AND MYOGENIN

The myogenic basic helix-loop-helix transcription factors, Myf5, MyoD, myogenin and MRF4, play key roles in skeletal muscle development(1,2) . All of them induce myogenic differentiation in cultured non-muscle c ells, suggesting that they might be functionally redundant. But the ge nes are expressed at different times during embryogenesis(3-6) and mic e carrying a mutation in any of the genes have different phenotypes(7- 13). A rib cage defect was observed in Myf5-deficient mice, which die perinatally(7). We investigated whether the rib cage defect was due to the failure of the early activation of the gene or to the unique inte ractions of Myf5 with specific downstream targets. For this we inserte d a myogenin complementary DNA into the Myf5 locus by homologous recom bination ,which simultaneously disrupted Myf5 function. We report here that mice homozygous for this myogenin gene knock-in (ki) developed a normal rib cage and were viable, therefore demonstrating functional r edundancy of Myf5 and myogenin for rib formation.