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

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