title: A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity.
abstract: The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.
authors.affiliation: School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Otto
authors.forename: Raymond
authors.initials: R
authors.lastname: Macharia
authors.forename: Antonios
authors.initials: A
authors.lastname: Matsakas
authors.forename: Petr
authors.initials: P
authors.lastname: Valasek
authors.forename: Baljinder S
authors.initials: BS
authors.lastname: Mankoo
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
mesh_terms: D000818:Animals; D001835:Body Weight; D002452:Cell Count; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development*; D032448:Myoblasts, Skeletal / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C484194:Meox2 protein, mouse