Muscle Regeneration in mdx Mice: Resistance to Repeated Necrosis is Compatible with Myofiber Maturity

The regenerated muscle fibers of mdx dystrophic mice remain permanently centronucleated and show resistance to repeated necrosis. Searching for mechanisms that could induce such resistance, we studied whether mdx regenerated fibers differ from the original ones by having a smaller calibre or by showing a different histochemical typing. Moreover, since in several genetic diseases of skeletal muscle the deleterious effects of abnormal gene expression are suppressed in immature fibers, we studied the expression of developmental myosin heavy chain (d-MHC) as a marker of persistent immaturity in mdx regenerated fibers. Our results show that in mdx gastrocnemius: 1) the course of the disease is accompanied by a prevalent loss of large-calibre original fibers with relative preservation of small-calibre fibers. On the contrary, regenerated fibers tend to grow larger than the original ones, without showing repeated necrosis. 2) Type II fibers show a mild decrease in number but are still largely preponderant over type I fibers at 6 months. 3) Expression of d-MHC is absent in fully regenerated myofibers. In conclusion, while large calibre and type II fibers are more vulnerable among the original myofiber population, these factors do not interfere with viability o