title: Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats.
abstract: Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN(+/+) ) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTN(Δ/Δ) ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTN(Δ/Δ) rats demonstrated 20-33% increases in mass, 35-45% increases in fibre number, 20-57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTN(Δ/Δ) muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTN(Δ/Δ) rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling.
authors: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors: Christopher L
authors: CL
authors: Mendias
authors: Evan B
authors: EB
authors: Lynch
authors: Jonathan P
authors: JP
authors: Gumucio
authors: Michael D
authors: MD
authors: Flood
authors: Danielle S
authors: DS
authors: Rittman
authors: Douglas W
authors: DW
authors: Van Pelt
authors: Stuart M
authors: SM
authors: Roche
authors: Carol S
authors: CS
authors: Davis
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D013710:Tendons / Q000378:metabolism*
chemical_list: D055435:Myostatin
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