Genetic and Epigenetic Effects on Diaphyseal Morphology in Selectively Bred Mice with the Mini-Muscle Allele


Meeting Abstract

P2.72  Wednesday, Jan. 5  Genetic and Epigenetic Effects on Diaphyseal Morphology in Selectively Bred Mice with the Mini-Muscle Allele. WALLACE, IJ; GARLAND, T Jr; WALLACE, SA; MIDDLETON, KM; KELLY, SA; JUDEX, S; DEMES, B*; Stony Brook Univ.; Univ. of California, Riverside; Univ. of Pennsylvania; California State Univ., San Bernadino; Univ. of North Carolina, Chapel Hill; Stony Brook Univ.; Stony Brook Univ. bdemes@ms.cc.sunysb.edu

Artificial selection of mice resulted in a 2.7-fold increase in voluntary wheel running in 4 replicate selected (S) lines compared to 4 nonselected control (C) lines. In 3 lines, a Mendelian recessive allele (MM) was identified that halves hind limb muscle mass. Mice with the MM allele also have reduced hind limb bone diaphyseal dimensions. However, it is unclear whether slender diaphyses are a direct pleiotropic effect of the MM allele or an epigenetic phenomenon related to the interaction of bone and muscle. To examine this issue, we used microCT to test for differences in femoral diaphyseal morphology in female 1-week-old mice from an S line in which the MM phenotype has become fixed and one S and one C line in which the MM phenotype has never been observed. We reasoned that slender diaphyses among MM mice at this age would suggest a pleiotropic effect because differences in muscle mass between the lines are not yet observable at 1 week postnatal (Middleton et al. 2008. Integr Comp Biol 48:394-410). The results indicate that the diaphyses of MM mice are relatively more slender than those of the normal S mice, but are not significantly different from those of the C mice. Therefore, the slender bone phenotype characteristic of MM adults is not unequivocally present during perinatal development. However, pleiotropy cannot be ruled out, and the genetic and epigenetic influences on diaphyseal morphology in MM mice remain unresolved. Nevertheless, the variation detected among S lines is notable and may represent multiple solutions to selection for high locomotor activity (Garland et al. 2010, Proc R Soc: In press). Supported by the Leakey Foundation (IJW) and NSF IOB-0543429 (TG).

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