MODIFICATIONS IN MYOTENDINOUS JUNCTION SURFACE-MORPHOLOGY IN DYSTROPHIN-DEFICIENT MOUSE MUSCLE

Single muscle fibers from mdr mouse muscle, which is deficient in dyst rophin, 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, s ites at the muscle cell surface that are enriched in dystrophin and wh ere force is transmitted across the cell membrane. Muscle fibers from 4- and 6-week-old controls display nearly uniform surface morphology c haracterized by numerous digit-like processes at the myotendinous junc tion and nonjunctional surface membrane possessing distinct grooves at sites corresponding to underlying costameres. Mdx fibers at this stag e showed blunted myotendinous junctions with few digit-like processes, infrequent indistinct costameric markings, and holes in the cell memb rane. Cells from peak regenerating mdx muscle (6 weeks) showed surface morphology similar to 4-week mdx fibers, although the proportion of f ibers displaying extensive structural defects was reduced at 6 weeks. Completely regenerated mdx fibers (23 weeks) were indistinguishable fr om 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 st ructural defects characteristic of the majority of mdx fibers. However , fibers from 23-week-old control mice displayed an increased frequenc y of cells with poorly defined junctional processes and surface striat ions. These findings indicate that the fibers displaying extensive dis ruption of surface features, which are most commonly observed in 4-wee k mdx mice at peak necrosis, are necrotic fibers. Specific defects, su ch as the reduction in myotendinous junction folding, loss of costamer es, and increased occurrence of membrane holes, are observed in the ma jority of mdx fibers at all ages. Thus, these defects are more directl y attributable to dystrophin's absence because their frequency of occu rrence is independent of the stage of necrosis and regeneration. (C) 1 994 Academic Press, Inc.