Muscular dystrophy in the mdx XXXX is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia.

@entity1603 @entity39 @entity19 @entity6286 @entity1555 @entity164
BACKGROUND: Preclinical testing of potential therapies for @entity1555 ( @entity1555 ) is conducted predominantly of the mdx @entity19 . But lack of a detailed quantitative description of the pathology of this animal limits our ability to evaluate the effectiveness of putative therapies or their relevance to @entity1555 . METHODS: Accordingly, we have measured the main cellular components of muscle growth and regeneration over the period of postnatal growth and early pathology in mdx and @entity164 ( @entity164 ) @entity19 ; @entity6286 binding is used as a measure of fibre size, myonuclear counts and @entity1603 labelling as records of myogenic activity. RESULTS: We confirm a two-phase postnatal growth pattern in @entity164 muscle: first, increase in myonuclear number over weeks 1 to 3, then expansion of myonuclear domain. Mdx muscle growth lags behind that of @entity164 prior to overt signs of pathology. Fibres are smaller, with fewer myonuclei and smaller myonuclear domains. Moreover, satellite cells are more readily detached from mdx than @entity164 muscle fibres. At 3  weeks, mdx muscles enter a phase of florid myonecrosis, accompanied by concurrent regeneration of an intensity that results in complete replacement of pre-existing muscle over the succeeding 3 to 4  weeks. Both @entity164 and mdx muscles attain maximum size by 12 to 14  weeks, mdx muscle fibres being up to 50% larger than those of @entity164 as they become increasingly branched. Mdx muscle fibres also become hypernucleated, containing twice as many myonuclei per sarcoplasmic volume, as those of @entity164 , the excess corresponding to the number of centrally placed myonuclei. CONCLUSIONS: The best-known consequence of lack of dystrophin that is common to @entity1555 and the mdx @entity19 is the conspicuous @entity39 and regeneration of muscle fibres. We present protocols for measuring this in terms both of loss of muscle nuclei previously labelled with @entity1603 and of the intensity of myonuclear labelling with @entity1603 administered during the regeneration period. Both measurements can be used to assess the efficacy of putative antinecrotic agents. We also show that lack of dystrophin is associated with a number of previously unsuspected abnormalities of muscle fibre structure and function that do not appear to be directly associated with myonecrosis.
