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Duchenne muscular dystrophy and the mdx mouse myopathies reflect a lack of dystrophin in muscles. However, both contain sporadic clusters of revertant fibers (RFs) that express dystrophin. RF clusters expand in size with age in mdx mice. To test the hypothesis that the expansion of clusters is achieved through the process of muscle degeneration and regeneration, we analyzed muscles of mdx mice in which degeneration and regeneration were inhibited by the expression of micro-dystrophins or utrophin transgenes. Postnatal RF expansion was diminished in direct correlation to the protective effect of the transgene expression. Similarly, expansion of RFs was inhibited when muscle regeneration was blocked by irradiation. However, in irradiated muscles, irradiation-tolerant quiescent muscle precursor cells reactivated by notexin effectively restored RF expansion. Our observations demonstrate that revertant events occur initially within a subset of muscle precursor cells. The proliferation of these cells, as part of the regeneration process, leads to the expansion of RF clusters within degenerating muscles. This expansion of revertant clusters depicts the cumulative history of regeneration, thus providing a useful index for functional evaluation of therapies that counteract muscle degeneration.

Original publication

DOI

10.1242/jcs.03000

Type

Journal article

Journal

J Cell Sci

Publication Date

01/07/2006

Volume

119

Pages

2679 - 2687

Keywords

Animals, Dystrophin, Elapid Venoms, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Mice, Transgenic, Muscle Fibers, Skeletal, Muscles, Muscular Dystrophy, Duchenne, Myoblasts, Neurons, Nitric Oxide Synthase, Regeneration, Sarcolemma, Utrophin, Whole-Body Irradiation