Meeting Abstract

P1.74  Saturday, Jan. 4 15:30  A novel intronic SNP in the Myosin heavy polypeptide 4 gene is responsible for the Mini-Muscle phenotype characterized by major reduction in hindlimb muscle mass in mice KELLY, S.A.*; BELL, T.A.; SELITSKY, S.R.; BUUS, R.J.; HUA, K.; WEINSTOCK, G.M.; GARLAND, JR., T.; PARDO-MANUEL DE VILLENA, F.; POMP, D.; Ohio Wesleyan Univ.; Univ. of North Carolina, Chapel Hill; Univ. of North Carolina, Chapel Hill; Univ. of North Carolina, Chapel Hill; Univ. of North Carolina, Chapel Hill; Washington Univ., St. Louis; Univ. of California, Riverside; Univ. of North Carolina, Chapel Hill; Univ. of North Carolina, Chapel Hill sakelly@owu.edu

Replicated artificial selection for high levels of voluntary wheel running in an outbred strain of mice favored an autosomal recessive allele whose primary phenotypic effect is a 50% reduction in hindlimb muscle mass. Within the High Runner (HR) lines of mice, the numerous pleiotropic effects (e.g., larger hearts, reduced total body mass and fat mass, longer hindlimb bones) of this hypothesized adaptive allele include functional characteristics that facilitate high levels of voluntary wheel running (e.g., doubling of mass-specific muscle aerobic capacity, increased fatigue resistance of isolated muscles, longer hindlimb bones). Previously, we created a backcross population suitable for mapping the responsible locus. We phenotypically characterized the population and mapped the Minimsc locus to a 2.6-Mb interval on MMU11 a region containing ~100 known or predicted genes. Here, we present a novel strategy to identify the genetic variant causing the mini-muscle phenotype. Using high-density genotyping and whole-genome sequencing of key backcross individuals and HR mice with and without the mini-muscle mutation, from both recent and historical generations of the HR lines, we show that a SNP representing a C to T transition located in a 709 bp intron between exons 11 and 12 of the Myosin, heavy polypeptide 4, skeletal muscle gene (Myh4; position 67,244,850 on MMU11; assembly, Dec. 2011, GRCm38/mm10; ENSMUSG00000057003) is responsible for the mini-muscle phenotype, Myh4^Minimsc.