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Effects of the Compact Mutant Myostatin Allele Mstn Cmpt-dl1Abc Introgressed into a High Growth Mouse Line on Skeletal Muscle Cellularity

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Abstract

The murine myostatin mutation MstnCmpt-dl1Abc (Compact; C) was introduced into an inbred mouse line with extreme growth (DUHi) by marker-assisted introgression. To study the allelic effects on muscle fibre hyperplasia and hypertrophy, myonuclear proliferation, protein accretion, capillary density, and muscle fibre metabolism, samples from M. rectus femoris (RF) and M. longissimus dorsi (LD) muscles of animals wild-type (+/+), heterozygous (C/+), and homozygous (C/C) for the MstnCmpt-dl1Abc allele were examined by histological and biochemical analyses. Homozygous C/C mice exhibited lower body (−12%) but higher muscle weights (+38%) than ++ mice. Total muscle fibre number was increased (+24%), whereas fibre size was not significantly affected. Protein and DNA concentrations and DNA:protein ratios as well as specific CK activity remained unchanged for higher mass muscle implying increases in the total contents of DNA and muscle specific protein. Fibre type distribution was markedly shifted to the white glycolytic muscle fibres (+16–17% units) at the expense of red oxidative fibres. Capillary density was substantially lower in C/C than in ++ mice as seen by lower number of capillaries per fibre (−35%) and larger fibre area per capillary (+77%). However, the MstnCmpt-dl1Abc allele was partially recessive in heterozyogous C/+ mice for both fibre type frequencies and capillary density. The results show that hypermuscularity caused by mutations in the myostatin gene results from muscle fibre hyperplasia rather than hypertrophy, and from balanced increases in myonuclear proliferation and protein accretion. However, capillary supply is adversely affected and muscle metabolism shifted towards glycolysis, which could have negative consequences for physical fitness.

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Rehfeldt, C., Ott, G., Gerrard, D.E. et al. Effects of the Compact Mutant Myostatin Allele Mstn Cmpt-dl1Abc Introgressed into a High Growth Mouse Line on Skeletal Muscle Cellularity. J Muscle Res Cell Motil 26, 103–112 (2005). https://doi.org/10.1007/s10974-005-1099-7

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