Ultrastructure of the skeletal muscle in the X chromosome-linked dystrophic (mdx) mouse. Comparison with Duchenne muscular dystrophy.
Ultrastructurally there are some clear differences in the pathology of muscle in X chromosome-linked muscular dystrophy of the mouse (mdx) and Duchenne muscular dystrophy (DMD). In particular the mouse muscle does not become infiltrated by large aggregations of connective tissue. It has been proposed that the differences are due to secondary biochemical changes consequent on the absence of dystrophin in both conditions. If this is the case, attention should be directed to the earliest ultrastructural changes held in common by both disorders. The most conspicuous of these, preceding myofibril breakdown, is dilation of the sarcoplasmic reticulum. Any physiological link between this and the absence of dystrophin remains to be determined. We suggest that in the mdx mouse, the widespread myofibre necrosis occurring at 3-4 weeks is triggered by increased mechanical demands causing the lack of dystrophin to become critical at this time. Subsequent regeneration of the myofibres appears to be almost completely successful. The ultimate failure of regeneration in DMD, in contrast, may be due to an additional factors acting in DMD exacerbating the lack of dystrophin. This additional factor may be associated with the plasma membrane lesions (not seen in mdx). Alternatively there may be factors present in the mouse that compensate for the lack of dystrophin. It is pointed out that to understand better the different processes occurring in mdx and DMD we need to learn more about the factors which control the balance between the growth of muscle and the growth of connective tissue in both normal and pathological human and mouse muscle.
Cullen
M J
MJ
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle-upon-Tyne, UK.
Jaros
E
E
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009132:Muscles / Q000648:ultrastructure*; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000473:pathology; D014960:X Chromosome