STUDIES ON THE EVOLUTION AND FUNCTION OF DIFFERENT FORMS OF THE MOUSE MYOGENIC GENE MYO-D1 AND UPSTREAM FLANKING REGION

The product of the murine Myo-D1 gene is able to initiate the complete sequence of genetic events required for formation of skeletal muscle. Because efficiency of regeneration of skeletal muscle is more pronounced in SJL/J mice, as compared to other strains, differences in the structure of Myo-D1 and the upstream regulatory region were sought to determine whether efficiency of tissue repair was influenced by the structure of the gene itself. Analysis of the restriction-fragment length polymorphism (RFLP) of genomic DNA from SJL/J and different sub-strains of mouse indicated that there are at least three different structural forms of Myo-D1, one of which is unique to SJL/J mice and may have been derived from a double recombinational event involving founder forms of Myo-D1. The unique form of Myo-D1 in SJL/J mice also exhibits a PvuII RFLP upstream from the gene, which may reflect some form of rearrangement or variation in methylation of a potential Myo-D1-binding region. Reference to the size of fragments hybridising with the Myo-D1 probe, following digestion of genomic DNA with TaqI, suggests that in most tissues, adenine residues within Myo-D1 may be extensively methylated. Segregation of Myo-D1 allotypes with response to mechanical injury to skeletal muscle in F2 offspring derived from SJL/J and BALB/c parental strains reveals that increased efficiency of tissue repair is associated with the SJL/J type of Myo-D1 gene. These observations provide new approaches to investigation of genetic control of tissue regeneration and cellular differentiation and proliferation in general.