A role for caveolin-3 in the pathogenesis of the mdx mouse

[摘要] Duchenne muscular dystrophy (DMD) is a muscle-wasting disease caused by the loss of sarcolemmal protein dystrophin. In DMD and the mouse model of the disease mdx, there is an increase in an associated protein, caveolin-3. In this study, mdx mice with deficiencies in caveolin-3 were generated to allow a distinction to be made between the pathology caused by the loss of dystrophin and that caused by an excess of caveolin-3. It was found that in late gestation embryos, there were perturbations in skeletal muscle stem cell populations and depletion of respiratory muscles in mdx and mdx/cav3\(^{+/-}\), both of which were more severe in mdx/cav3\(^{+/-}\) embryos. In post natal skeletal muscles, there was a trend in that the level of regeneration, believed to be indicative of previous degeneration, was consistently greater in mdx than mdx/cav3\(^{+/-}\). Taken together it would appear whereas increased caveolin-3 may compensate for the lack of dystrophin in embryonic mdx muscle; post natally, it may contribute to the muscle regeneration observed in mdx. The data presented in this thesis should help towards clarifying the contribution of caveolin-3 in the pathogenesis of DMD and in doing so expand on the understanding of the molecular aetiology of the disease.

[发布机构] University:University of Birmingham;Department:School of Biosciences

[关键词] Q Science;QH Natural history;QH301 Biology