Development of muscle pathology in canine X-linked muscular dystrophy. II.Quantitative characterization of histopathological progression during postnatal skeletal muscle development

We have characterized the time course of muscle pathology development durin g the postnatal maturation of quadriceps and tibialis anterior muscle in dy strophic golden retriever dogs. We determined the percentages of degenerati ng, regenerating, calcium-positive, hypercontracted, albumin-positive, and C3 complement fraction-positive muscle fibers and the extent of connective tissue proliferation in animals from neonate to adult. Necrotic fibers incr eased from days 2 to 30, decreased at 60 days (to 0.8%) and increased in ol der animals to a stable level of around 2%. Hypercontracted fibers peaked a t 15 days (19.1%) and declined to 3.7% in adults. Regenerating fibers were numerous at 15 and 30 days (10%), declined at 60 days to 4.7% and declined further in adults. Calcium- and albumin-positive fibers peaked at 30 days ( 6.5% and 13.8%, respectively) acid then declined to around 3% and 5%, respe ctively, in older dogs. In dystrophic dogs, the extent of fibrosis was sign ificantly greater on 15 days than in controls, but did not then increase wi th age. In carriers, calcium- and albumin-positive fibers always expressed dystrophin abnormally. Muscle damage occurs before completion of muscle mat uration in dystrophic dogs. while necrosis and hypercontraction remain stab le in adults, fiber regeneration declines to very low levels. In contrast t o Duchenne muscular dystrophy, muscle fibrosis in the muscle studied does n ot increase with age.