Lack of myostatin results in excessive muscle growth but impaired force generation

Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1835-40. doi: 10.1073/pnas.0604893104. Epub 2007 Jan 31.

Abstract

The lack of myostatin promotes growth of skeletal muscle, and blockade of its activity has been proposed as a treatment for various muscle-wasting disorders. Here, we have examined two independent mouse lines that harbor mutations in the myostatin gene, constitutive null (Mstn(-/-)) and compact (Berlin High Line, BEH(c/c)). We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles. In addition, Mstn(-/-) muscle contracted and relaxed faster during a single twitch and had a marked increase in the number of type IIb fibers relative to wild-type controls. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Contraction / genetics
  • Muscle Contraction / physiology*
  • Muscle Development / genetics
  • Muscle Development / physiology*
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / physiology
  • Muscle, Skeletal / physiopathology*
  • Myostatin
  • Oxidation-Reduction
  • Transforming Growth Factor beta / deficiency*
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / physiology

Substances

  • Mstn protein, mouse
  • Myostatin
  • Transforming Growth Factor beta