A loss of muscle mass and strength with aging or disease leads to a compromised quality of life. Therefore, it is important to understand the mechanisms underlying muscle function. The present proposal will shed light on largely unknown mechanisms underlying the effects of genetic variation on important properties of muscle fibres (i.e. their number, size, type) which in turn contribute to muscle mass and contractility. A multi-pronged approach will be used to explore soleus and extensor digitorum longus (EDL) muscle fiber properties in a variety of genetic contexts: in six inbred mouse strains, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, PWD/PhJ (Specific Aim 1); in two congenic strains, Psl1.H3 and Psl1.E and the C57BL/6J host that have been used to fine map the Skmw11 locus, which influences muscle weight, (Specific Aim 2); and in two segregating populations, F2 and F34, derived from the inbred strains (LG/J and SM/J) selected for differences in body weight (and which differ markedly in muscle weight) and that have been extensively genotyped (Specific Aim 3). The following outcomes are expected: Specific Aim 1 will identify strains contrasting in fibre properties. This information will help us select strains for mapping genes underlying the differences. Specific Aim 2 will explore the role of the Skmw11 locus on fibre properties and we may be able to map genes affecting fibre properties to the congenic regions. Specific Aim 3 will permit us to map and refine quantitative trait loci (QTL) affecting muscle fibre properties in a population of mice derived from parents with large differences in muscle weight.
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