Absence of desmin slightly prolongs myoblast proliferation and delays fusion in vivo in regenerating grafts of skeletal muscle

The expression of desmin, a muscle-specific intermediate filament protein, is upregulated during skeletal myogenesis, but its role in the myogenic pro cess is unclear. Postnatal skeletal muscle regeneration occurs to completio n in desmin null (-/-) mice, however, only late time points (i.e., days 7 a nd 21) in the myogenic process have been examined. This study observes the early events in skeletal muscle regeneration (i.e., from 3 days) in desmin (-/-) mice. Whole muscle autografts were performed in desmin (-/-) and cont rol normal (Balb/c) mice. Muscle samples were taken on days 3, 5, 6, 7, 8, 9 and 11 after transplantation? and regeneration was assessed by graft morp hology, patterns of cell proliferation and quantitation of myotube numbers. At day 5 myotube formation was delayed in the desmin (-/-) grafts compared to the normal controls. Immunohistochemical analysis of proliferating cell nuclear antigen demonstrated a very high proportion of proliferating cells in the periphery of desmin (-/-) whole muscle grafts at day 5 compared to the controls, where mitosis in this area was negligible. This strongly indi cates t hat myoblast proliferation is prolonged during postnatal myogenesis in the absence of desmin. By day 6 there was no marked morphological diffe rence between desmin (-/-) and normal control whole muscle grafts, although the zonal pattern of myoblast replication was slightly delayed in the desm in (-/-) mice until day 8. These results indicate a slightly extended phase of myoblast proliferation with delayed fusion in vivo in mature regenerati ng desmin (-/-) skeletal muscle.