Meeting Abstract

40.5  Jan. 6  Phenotypic effects of the “mighty mini-muscle” allele in a large HR x C57Bl/6J backcross HANNON, R,M*; KELLY, S,A; MIDDLETON, K,M; KOLB, E,M; POMP, D; GARLAND JR., T; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of California, Riverside; Univ. of North Carolina, Chappel Hill; Univ. of California, Riverside rhann002@student.ucr.edu

Beginning with a base population of outbred Hsd:ICR mice, we produced four replicate lines of mice selected for high voluntary wheel-running (S lines), while also maintaining four non-selected lines as controls (C lines). During the experiment we discovered an apparent Mendelian recessive allele whose main phenotypic effect is to reduce hindlimb muscle mass by approximately 50%. Analyses show that the allele has been favored by the selection protocol, and it eventually went to fixation in one of the selected lines. Individuals homozygous for this allele exhibit various pleiotropic effects, including doubled mass-specific muscle aerobic capacity, larger hearts, lungs, livers, spleens, and kidneys, and longer, thinner hindlimb bones. To begin mapping of the genomic location at which the mutation resides, we crossed the fixed mini-muscle line to the inbred C57Bl/6J strain, and backcrossed the F1 to the mini-muscle line. We dissected approximately 400 backcross mice and found a 50:50 ratio of normal:mini-muscle phenotype, with no overlap in relative muscle mass, thus confirming the recessive nature of the allele on this new genetic background and indicating that this backcross population is highly suitable for eventual linkage mapping of the chromosomal position of the mutant allele. In the backcross population, mini-muscle individuals ran more on days 5+6 of a 6-day exposure to wheels, at higher average and maximum speeds, but not for more minutes per day. Mini-individuals were smaller in body mass. After adjusting for variation in body mass, mini-muscle individuals had relatively larger ventricles and spleens. Supported by NSF grant IOB-0543429 to T.G.