Modifications In Myotendinous Junction Surface-morphology In Dystrophin-deficient Mouse Muscle

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Experimental And Molecular Pathology




Single muscle fibers from mdr mouse muscle, which is deficient in dystrophin, and control mouse muscle, containing dystrophin, were compared by scanning electron microscopy. In particular, comparisons were made of the surface morphology at myotendinous junctions and costameres, sites at the muscle cell surface that are enriched in dystrophin and where force is transmitted across the cell membrane. Muscle fibers from 4- and 6-week-old controls display nearly uniform surface morphology characterized by numerous digit-like processes at the myotendinous junction and nonjunctional surface membrane possessing distinct grooves at sites corresponding to underlying costameres. Mdx fibers at this stage showed blunted myotendinous junctions with few digit-like processes, infrequent indistinct costameric markings, and holes in the cell membrane. Cells from peak regenerating mdx muscle (6 weeks) showed surface morphology similar to 4-week mdx fibers, although the proportion of fibers displaying extensive structural defects was reduced at 6 weeks. Completely regenerated mdx fibers (23 weeks) were indistinguishable from fibers of 6-week-old mdx mice. In control mice, only similar to 6% of the fibers examined from 4- or 6-week-old mice showed any of the structural defects characteristic of the majority of mdx fibers. However, fibers from 23-week-old control mice displayed an increased frequency of cells with poorly defined junctional processes and surface striations. These findings indicate that the fibers displaying extensive disruption of surface features, which are most commonly observed in 4-week mdx mice at peak necrosis, are necrotic fibers. Specific defects, such as the reduction in myotendinous junction folding, loss of costameres, and increased occurrence of membrane holes, are observed in the majority of mdx fibers at all ages. Thus, these defects are more directly attributable to dystrophin's absence because their frequency of occurrence is independent of the stage of necrosis and regeneration.