PHENOTYPE OF DYSTROPHINOPATHY IN OLD MDX MICE

Background: Mdx mutant mice, like patients with Duchenne Muscular Dyst rophy (DMD), lack dystrophin, a subsarcolemmal protein, that results i n myofiber necrosis. However young mdx mice, in contrast to DMD childr en, exhibit a successful muscle regeneration and not an extensive fibr osis. Methods: Old mdx mice were monitored clinically up to their spon taneous death, and most of their organs were studied histologically to look for differences with those of the wild C57BL/10 mice strain. Res ults: In old mdx mice (at least 20 months of age), we report clinical and pathological features of muscular dystrophy, i.e., progressive mot or weakness and loss of myofibers replaced by extensive connective tis sue, similar to the phenotype of dystrophinopathy observed in DMD pati ents, Various degrees of dystrophic involvement were observed in cardi ac, respiratory, postural, and hindlimb skeletal mdx muscles and also in smooth muscles of the digestive and urinary tracts. No gross histol ogical abnormalities were found in other tissue than muscular tissue. Conclusions: Late in life, mdx mice develop a muscular dystrophy close to DMD dystrophinopathy. We suggest that the study of the effects of ageing in mdx mice would give clues to better understand the pathophys iology of DMD. (C) 1995 Wiley-Liss, Inc.