The influence of sex hormones on cardiac and skeletal muscle function in the MDX mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a fatal recessive genetic human disease affecting one in 3500 live male births. DMD is progressive, there is no cure, and patients typically die of respiratory or cardiac failure in their second decade of life. Clinical disease symptoms are exacerbated at the onset of puberty and the physiological basis of this is unknown. The mdx mouse is the preferred experimental animal model of DMD, although aspects of the model remain poorly understood. This dissertation characterises physiological and histological features of the dystrophic mdx mouse in response to manipulations of hormonal status including testosterone treatment, surgical castration, and oestrogen treatment. Sex-specific differences in the mdx were also examined. Furthermore, physiological and histological features of the dystrophic mdx mouse model throughout the mdx lifespan were evaluated. Cardiac muscle contractility, left atrial response to exogenous calcium, and the contractile properties of both fast-twitch (EDL)and slow-twitch (SOL) skeletal muscles were examined in male mdx mice ranging from 14 to 330 days of age. Testosterone treatment produced a nonsignificant trend towards a dose-dependent decrease in both basal and maximal left atrial contractility in the mdx. Surgical castration produced no significant cardiac effects within mouse strains. The mdx castrates had a 45% lower maximum atrial force of contraction than control castrates (p