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 whole muscle grafts in MyoD(-/-) and control BALB/c adult mice using immunohistochemistry and electron microscopy. Immunohistochemistry with antibodies to desmin and myosin revealed a striking delay by about 3 days in the formation of myotubes in MyoD(-/-) autografts compared with BALB/c mice. However, myotube formation was not prevented, and autografts in both strains appeared similar by 8 days. Electron microscopy confirmed myotube formation in 8- but not 5-day MyoD(-/-) grafts. This pattern was not influenced by cross-transplantation experiments between strains examined at 5 days. Antibodies to proliferating cell nuclear antigen demonstrated an elevated level of replication 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 proliferation of the MyoD(-/-) myoblasts. Overall, although muscle regeneration was delayed it was not impaired in MyoD(-/-) mice in this model.
White
J D
JD
Department of Anatomy and Human Biology, the University of Western Australia, Nedlands, Western Australia. jwhite@anhb.uwa.edu.au
Scaffidi
A
A
Davies
M
M
McGeachie
J
J
Rudnicki
M A
MA
Grounds
M D
MD
D000818:Animals; D002455:Cell Division; D002459:Cell Fusion; D003893:Desmin / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure*; D017570:MyoD Protein / Q000235:genetics*; D012038:Regeneration; D014182:Transplantation, Autologous
D003893:Desmin; D017570:MyoD Protein