Development of muscle pathology in canine X-linked muscular dystrophy. I. Delayed postnatal maturation of affected and normal muscle as revealed by myosin isoform analysis and utrophin expression

Canine X-linked muscular dystrophy (CXMD) is genetically homologous to Duch enne muscular dystrophy and shares the severe myopathy and lethal clinical development of the human disease. We used immunohistochemistry to character ize the time course of postnatal expression of adult fast, adult slow and d evelopmental myosin in the muscle of CXMD dogs, carriers and healthy contro ls. We also characterized the expression of utrophin and dystrophin. This d etailed immunolocalization study confirmed that postnatal muscle maturation is delayed in normal dogs compared to other animals and humans, and is onl y achieved at around 60 days. In CXMD dogs major derangement of myosin expr ession became evident from about 15 days; there was a selective loss of fib ers expressing fast myosin and persistence of developmental fibers compared to controls. In carriers, the proportion of dystrophin-deficient fibers, w hich mainly expressed fast myosin, decreased with age. In controls and carr iers utrophin was absent from muscle fiber surfaces in 2-day-old animals bu t present between 15 and 30 days, to mostly disappear by 60 days. In dystro phic animals, sarcolemmal expression of utrophin was more marked and persis tent. That immature neonatal muscle from control dogs normally contains sar colemmal utrophin may have implications for the success of utrophin up-regu lation therapy to correct the dystrophic phenotype. The data of this study provide important baseline information for further studies on the developme nt and progression of pathological changes in the muscle of CXMD dogs.