Histochemical and structural analyses of the phenotypic expression of the dystrophic gene in the [formula omitted] and the [formula omitted] mice

Abstract

Although both slow- and fast-twitch fibers of dystrophic genotype are affected by the disease hereditary muscular dystrophy, our histochemical evidence indicates a differential temporal involvement of different fiber types in the two strains of dystrophic mice investigated. Whereas in the 129 ReJ dy dy mice the disease is expressed early in white, fast-twitch glycolytic fibers, in the C57BL 6J dy 2J dy 2J mice the primary expression of the disease is noted in red, slow-twitch oxidative fibers. In the former, wasting progresses rapidly in leg muscles characterized by a large proportion of fast-twitch fibers; in the latter, there is a prolonged maintenance of the integrity of regions rich in these fibers. Of equal importance with the C57BL 6J dy 2J dy 2J mouse is the detection of small foci of destruction in regions rich in slow-twitch fibers as early as 2 to 3 weeks postnatally; wasting of these fibers ensues rapidly. Thus, in both strains, the fibers which are affected primarily show early alterations with a subsequent rapid progression of disease characteristics and the fibers which seem secondarily affected remain intact for prolonged periods. Our observations suggest an important role of the dy 2J dy 2J mouse as a “transitional” model to investigate a relationship between genotypically dystrophic muscle in which the phenotypic expression of the disease is present and genotypically dystrophic muscle spared phenotypic signs of the disease. The latter, characterized by multiple innervation, is never challenged to alter its metabolic or physiologic behavior during ontogeny.