Mdx mice, which lack dystrophin, were examined for changes in the properties of muscle fibers in the growth process of the masseter muscle at the morphological, protein and transcriptional levels. The slow-type isoform, MyHC-1, and the fast-type isoforms, MyHC-2a, MyHC-2d and MyHC-2b, were examined at the protein and the transcriptional level. Morphological examination showed that in the mdx mouse masseter muscle, degeneration, necrosis, and regeneration occurred, particularly at the age of 4 weeks, and many regenerated muscle fibers with centrally located nuclei were observed at the age of 9 weeks. The results of examination at the protein and the transcriptional level showed that in the process of muscle fiber degeneration, necrosis, and regeneration, the mdx mouse masseter muscle acquires muscle fiber characteristics entirely different from those in the normal mouse masseter muscle. In particular, MyHC-1, which is rarely found in normal mice, was very strongly expressed.

The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that the lack of dystrophin causes muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic muscle fibers are replaced by regenerated muscle fibers by 4 weeks after birth. A recent study indicated the possibility that mitochondria-mediated intracellular stress, a phenomenon similar to apoptosis, may be produced during muscle fiber necrosis, but did not analyze endoplasmic reticulum-mediated intracellular stress.Therefore, we examined the expression of the caspase-12 gene involved in the endoplasmic reticulum stress pathway and the Bax, caspase-9, and caspase-3 genes involved in the mitochondrial stress pathway in the mdx masseter muscle. We found over-expression of caspase-12 in cells at 2-3 weeks after birth when muscle fiber necrosis was not prominent. This suggests that s tress occurs in the endoplasmic reticulum to maintain cell morphology in the absence of dystrophin. In addition, Bax was abundantly expressed in the mdx masseter muscle at 3 weeks after birth, and the expression of caspase-9 and -3 was prominent at 3-4 weeks after birth when necrosis and regeneration were marked. These results indicate that endoplasmic reticulum and mitochondrial stresses are produced during necrosis of 3 the mdx masseter muscle, and suggest that these events are a phenomenon similar to apoptosis.