Small-caliber skeletal muscle fibers do not suffer deleterious consequences of dystrophic gene expression

Abstract

In Duchenne dystrophy and in the genetic dystrophies of CHF-147 hamsters and MDX mice, the fundamental deleterious consequence of dystrophic gene expression is segmental necrosis of skeletal muscle fibers. The nature of the gene defects and the pathogenesis of muscle fiber damage are not known. However, clinical and experimental evidence indicates that muscle fibers, whose girth is below a certain level (estimated at approximately 20-25 microns in diameter in dystrophic hamsters and MDX mice) are not susceptible to necrosis. This apparent "immunity" has been observed in muscle fibers that are naturally of small girth (such as those in extraocular muscles), and in fibers that were prevented from growing normally by experimental procedures (hamsters and mice) or by pathological processes (Duchenne patients). The cellular or molecular basis by which small-caliber muscle fibers are resistant to the necrotizing effect of the dystrophic gene expression remains unknown. In small-caliber muscle fibers, the normal contraction-related mechanical strains per unit surface area are relatively less than in larger fibers; this could explain their relative resistance to necrosis in some dystrophies.