UTROPHIN-DYSTROPHIN-DEFICIENT MICE AS A MODEL FOR DUCHENNE MUSCULAR-DYSTROPHY

The absence of dystrophin at the muscle membrane leads to Duchenne mus cular dystrophy (DMD), a severe muscle-wasting disease that is inevita bly fatal in early adulthood. In contrast, dystrophin-deficient mdx mi ce appear physically normal despite their underlying muscle pathology. We describe mice deficient for both dystrophin and the dystrophin-rel ated protein utrophin. These mice show many signs typical of DMD in hu mans: they show severe progressive muscular dystrophy that results in premature death, they have ultrastructural neuromuscular and myotendin ous junction abnormalities, and they aberrantly coexpress myosin heavy chain isoforms within a fiber. The data suggest that utrophin and dys trophin have complementing roles in normal functional or developmental pathways in muscle. Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model f or rapid evaluation of gene therapy strategies.