c-Met affects the number of type 2 fibres in mouse soleus

The Biomedical Basis of Elite Performance 2016 (Nottingham, UK) (2016) Proc Physiol Soc 35, C09

Oral Communications: c-Met affects the number of type 2 fibres in mouse soleus

A. Lionikas1, G. Riboni Verri1, M. N. Podaru1, N. George1, S. I. Wenham1, P. N. Hamond1, J. Nicod2, D. A. Blizard3

1. School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom. 2. Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. 3. Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania, United States.

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Skeletal muscle is characterized by extensive individual variability; muscle mass can range between 35 and 50 kg in healthy young males (Wolfe 2006). This variability is a function of the difference in the cross-sectional area (CSA) of muscle fibres and/or their number; the latter can also differ 2-fold (MacDougall et al. 1984). Approximately half of the variability in muscle properties is due to poorly understood genetic factors (Silventoinen et al. 2008). Elucidation of the underlying genetics will help understand the mechanisms limiting athletic performance and adaptation to training. The laboratory mouse also exhibits extensive variability in muscle properties (Lionikas et al. 2013) providing a useful research model. We employed a genome wide association study (GWAS) strategy to search for genes affecting muscle mass in CFW outbred mice. Mass (wet weight) of 4 selected muscles varied 2-fold in a population of ≈2,000 CFW mice. DNA for genotyping was extracted from tail biopsies collected after sacrifice. Twenty two quantitative trait loci (QTL) affecting this variability were mapped in the GWAS analysis (Nicod et al. submitted). A QTL on mouse chromosome 6 harboured only one gene which coded for c-Met protein. An Arg968Cys polymorphism present in CFW mice is likely to affect function of the protein and hence is a plausible basis for the QTL. The aim of the present study was to examine the effect of the Arg968Cys polymorphism on the properties of muscle fibres in selected CFW carriers of the Arg (n=26) or Cys (n=25) allele. The number and CSA of type 1 and type 2 fibres have been assessed in soleus muscle following ATPase staining. A 2-way ANOVA (sex (28 males, 23 females) and allele (Cys or Arg)) was used for statistical analysis. The main finding was that carriers of the Arg allele exhibit a significant increase (p<0.001) in type 2 fibres compared to those carrying Cys. The number of type 1 fibres was not allele-dependent (p=0.64). As the result, proportion of type 1 fibres is greater (p<0.01) in the Cys allele carriers. It has been known that c-Met plays a critical role in embryonic development of skeletal muscle. The present study reveals that variants of this gene can contribute to the differences in muscle mass observed in vivo. Furthermore, it indicates that the effect is primarily caused by the influence on the type 2 fibres. Fibre-type specific effects of c-Met help understand the role of genetic variability on muscle properties relevant to performance in athletic events and adaptation to training. Exploration of the remaining QTLs will further expand our understanding of the role of genetic mechanisms in determining muscle mass and function.



Where applicable, experiments conform with Society ethical requirements.

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