title: Morphology and myofiber composition of skeletal musculature of the forelimb in young and aged wild type and myostatin null mice.
abstract: Most current research into therapeutic approaches to muscle diseases involves the use of the mouse as an experimental model. Furthermore, a major strategy to alleviate myopathic symptoms through enhancing muscle growth and regeneration is to inhibit the action of myostatin (Mstn), a transforming growth factor-beta (TGF-beta) family member that inhibits muscle growth. Presently, however, no study has expanded the morphological analysis of mouse skeletal muscle beyond a few individual muscles of the distal hindlimb, through which broad conclusions have been based. Therefore, we have initially undertaken an expansive analysis of the skeletal musculature of the mouse forelimb and highlighted the species-specific differences between equivalent muscles of the rat, another prominently used experimental model. Subsequently, we examined the musculature of the forelimb in both young and old adult wild-type (mstn(+/+)) and myostatin null (mstn(-/-)) mice and assessed the potential beneficial and detrimental effects of myostatin deletion on muscle morphology and composition during the aging process. We showed that: (1) the forelimb muscles of the mouse display a more glycolytic phenotype than those of the rat; (2) in the absence of myostatin, the induced myofiber hyperplasia, hypertrophy, and glycolytic conversion all occur in a muscle-specific manner; and, importantly, (3) the loss of myostatin significantly alters the dynamics of postnatal muscle growth and impairs age-related oxidative myofiber conversion.
authors.affiliation: School of Biological Sciences, University of Reading, Reading, United Kingdom.
authors.forename: Mohamed I
authors.initials: MI
authors.lastname: Elashry
authors.forename: Anthony
authors.initials: A
authors.lastname: Otto
authors.forename: Antonios
authors.initials: A
authors.lastname: Matsakas
authors.forename: Salah E
authors.initials: SE
authors.lastname: El-Morsy
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D005552:Forelimb / Q000473:pathology*; D006019:Glycolysis; D006965:Hyperplasia; D006984:Hypertrophy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D055435:Myostatin / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism; D009929:Organ Size; D009928:Organ Specificity; D010641:Phenotype; D051381:Rats
chemical_list: D055435:Myostatin; D018995:Myosin Heavy Chains