Myotube formation is delayed but not prevented in MyoD-deficient skeletal muscle: Studies in regenerating whole muscle grafts of adult mice

We compared the time course of myogenic events in vivo in regenerating whol e muscle grafts in MyoD(-/-) and control BALB/c adult mice using immunohist ochemistry and electron microscopy. Immunohistochemistry with antibodies to desmin and myosin revealed a striking delay by about 3 days in the formati on of myotubes in MyoD(-/-) autografts compared with BALB/c mice. However, myotube formation was not prevented. and autografts in both strains appeare d similar by 8 days. Electron microscopy confirmed myotube formation in 8- but not 5-day MyoD(-/-) grafts. This pattern was not influenced by cross-tr ansplantation experiments between strains examined at 5 days. Antibodies to proliferating cell nuclear antigen demonstrated an elevated level of repli cation by MyoD(-/-) myoblasts in autografts, and replication was sustained for about 3 days compared with controls. These data indicate that the delay in the onset of differentiation and hence fusion is related to extended pr oliferation of the MyoD(-/-) myoblasts. Overall, although muscle regenerati on was delayed it was not impaired in MyoD(-/-) mice in this model.