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

Larner, Dean Paul (2012). A role for caveolin-3 in the pathogenesis of the mdx mouse. University of Birmingham. Ph.D.

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Abstract

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.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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