FORMATION PROCESS OF DYSTROPHIN-POSITIVE MUSCLE FIBERS FOLLOWING THE MYOBLAST TRANSPLANTATION TO MDX MICE.

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Dystrophin is a responsible protein of Duchenne muscular dystrophy(DMD) and is present at the protoplasmic surface of normal sarcolemma. Its absence is observed in DMD and mdx (mouse equivalent to DMD) muscles and is considered to be the cause of muscle fiber degeneration. To construct the subsarcolemmal undercoat in mdx muscle for the trial of therapy of the disease, myoblasts with normal dystrophy gene are injected into mdx mouse muscle. In this study we intended to elucidate the mechanism how dystrophin-positive fibers are constructed following myoblast transfer.We injected C2 myoblasts, a normal mouse muscle cell line, into the muscles of mdx nude mouse. This resulted in wide-spread necrosis of the injected muscle which was followed by regeneration. A large number of dystrophin-positive fibers appeared at the regeneration area. Isoformes of glucose-6-phosphate isomerase homodimer were used for the analysis, which are different in C2 and mdx cells. In dystrophin-positive muscle, a hybrid enzyme was observed, suggesting many of each fiber contain both normal and mdx muclei. Such hybrid fibers may not be resulted from uptake of C2 myoblasts to the intact mdx fibers, but from fusion of C2 myoblasts and mdx satellite cell generated on necrosis of the muscle fibers, considering the fiber formation process and the sizes of these fibers. In addition to this, the presence of muscle fibers made from fusion of C2 myoblasts cannot be excluded.