DYSTROPHY AND MYOGENESIS IN MDX DIAPHRAGM MUSCLE

In order to determine why the diaphragm is more severely affected by p rogressive dystrophy than limb muscles in the mdx mouse, we examined h ow regional variations in diaphragm dystrophy, the measures of disease and repair, proliferation by committed myogenic cells, and the expres sion of mitogenic basic fibroblast growth factor (bFGF) could contribu te to muscle-specific disease phenotypes. There were regional variatio ns in new myotube formation in the djaphragm, with disease more severe in crural than costal leaflets. New repair increased in hyperthyroidi sm without changes in accumulated repair, probably due to fiber loss. General proliferation was nearly twofold higher in limb than diaphragm mononuclear cells. Since only 2.5-8.4% of committed muscle precursors were proliferating, the higher proliferation by myf5+ myogenic cells in diaphragm did not account for muscle-specific differences, Prolifer ation by bFGF+ mononuclear cells and an immunogold labeling index for bFGF protein in diaphragm myoblasts were lower in diaphragm than limb muscle. In culture, mixed limb myoblast and fibroblasts contained more S phase cells than diaphragm cells, although myoblasts cycled similar ly between muscles. Therefore while muscle architecture and the format ion and number of new myotubes certainly affect disease phenotype, the differential outcome of regeneration in mdx diaphragm and limb muscle appears to be contributed by both nonmyogenic and myogenic cells. (C) 1998 John Wiley & Sons, Inc.