Alterations in fast and slow-twitch muscles of genetically dystrophic mice with special reference to parvalbumin

Muscular dystrophy is a genetic disease which affects the morphology, physiology and biochemical nature of the muscle fiber. This study was designed to examine the progressive effects of muscular dystrophy on the differentiation process of skeletal muscle. Chapter 1 examines the neonatal development of muscle spindles and their intrafusal fibers in the soleus and extensor digitorum longus (EDL) of genetically dystrophic mice according to histochemical, quantitative, and ultrastructural parameters. Despite alterations in the surrounding extrafusal fibers, muscle spindles and their intrafusal fibers appeared enzymatically and histologically unaffected in incipient stages of murine dystrophy. In the second chapter the distribution and concentration of parvalbumin (PV), a calcium-binding protein, in 32 and 2-week-old dystrophic mice was mapped by immunohistochemical and biochemical procedures. The number of parvalbumin-immunoreactive fibers was significantly reduced in the adult dystrophic EDL but slightly increased in the adult dystrophic soleus. No differences between strains were observed in the 2-week samples. These findings were supported by routine myosin ATPase histochemistry. Parvalbumin was isolated on SDS-PAGE gels and the concentration of PV was estimated by a RIA. These results confirmed the immunohistochemical data in that PV content was dramatically reduced in the adult dystrophic EDL and significantly increased in the dystrophic soleus. No changes were detected in the samples of the 2-week-old muscles. The similarity in the distribution and content of PV between the fast and slow dystrophic muscles at 32 weeks of age suggests an alteration in the distribution and phenotypic expression of fiber types in muscular dystrophy and supports the hypothesis that dystrophy alters the normal differentiation process of skeletal muscle.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat