INACTIVATION OF MYF-6 AND MYF-5 GENES IN MICE LEADS TO ALTERATIONS INSKELETAL-MUSCLE DEVELOPMENT

Myf-6, alternatively called MRF4 or herculin, is a member of a group o f muscle-specific transcription factors which also comprises Myf-5, my ogenin and MyoD. All family members show distinct expression patterns during skeletal muscle development and can convert a variety of cell l ines to myocytes. We disrupted the Myf-6 gene in mice to investigate i ts functional role in the network of regulatory factors controlling my ogenesis. Homozygous mice carrying the disrupted Myf-6 gene show prono unced down-regulation of Myf-5 transcription for reasons presently unk nown. Consequently, these mice represent a double knock-out model for Myf-6 and Myf-5. The mutants resemble most of the Myf-5 phenotype with aberrant and delayed early myotome formation and lack of distal rib s tructures. In addition, we find a reduction in the size of axial muscl es in the back. Apart from changes in the pattern of some contractile protein isoforms, the existing myofibers appear fairly normal. This su ggests that Myf-6 has no major role in the maturation of myotubes, as previously proposed. Our results provide evidence that skeletal myogen esis can proceed in the absence of two myogenic factors, Myf-5 and Myf -6, therefore they must exert largely non-redundant functions in vivo.