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Characterization of Myopathy in Mice Overexpressing Androgen Receptor in Skeletal Muscle

Although androgens are known to exert anabolic effects in skeletal muscle,
overexpression of androgen receptor (AR) selectively in this tissue causes androgen dependent motor deficits and muscular atrophy. The cellular and subcellular changes
underlying this phenotype are unknown. Therefore, this study aimed to elucidate the
ultrastructural and histologic changes accompanying myopathy and to determine the
importance of androgens and overexpression level for myopathic features. Transmission
electron microscopy revealed augmented mitochondrial content and reduced myofibril
width in androgen exposed transgenics. Additionally, male transgenics demonstrated
increased glycogen content. Histochemical analyses confirmed sex-specific changes in
glycogen content and revealed a surprising loss in the proportion of oxidative fibers in
symptomatic animals. However, increased mitochondrial content was confirmed by the
presence of ragged red fibers. Overexpression of AR in muscle fiber results in mitochondrial pathology and dysregulation of glycogen metabolism, possibly reflecting
normal but exaggerated function of androgens in skeletal muscle fibers.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/24609
Date27 July 2010
CreatorsMusa, Mutaz
ContributorsMonks, D. Ashley
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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