Quadrupling muscle mass in mice by targeting TGF-β signaling pathways

Se Jin Lee

Research output: Contribution to journalArticle

Abstract

Myostatin is a transforming growth factor-ß family member that normally acts to limit skeletal muscle growth. Mice genetically engineered to lack myostatin activity have about twice the amount of muscle mass throughout the body., and similar effects are seen in cattle, sheep, dogs, and a human with naturally occurring loss-of-function mutations in the myostatin gene. Hence, there is considerable interest in developing agents capable of inhibiting myostatin activity for both agricultural and human therapeutic applications. We previously showed that the myostatin binding protein, follistatin, can induce dramatic increases in muscle mass when overexpressed as a transgene in mice. In order to determine whether this effect of follistatin results solely from inhibition of myostatin activity, I analyzed the effect of this transgene in-myostatin-null mice. Mstn-/- mice carrying a follistatin transgene had about four times the muscle mass of wild type mice, demonstrating the existence of other regulators of muscle mass with similar activity to myostatin. The greatest effect on muscle mass was observed in offspring of mothers homozygous for the Mstn mutation, raising the possibility that either myostatin itself or a downstream regulator may normally be transferred from the maternal to fetal circulations. These findings demonstrate that the capacity for increasing muscle growth by manipulating TGF-ß signaling pathways is much more extensive than previously appreciated and suggest that muscle mass may be controlled at least in part by a systemic mode of action of myostatin.

Original languageEnglish (US)
Article numbere789
JournalPLoS One
Volume2
Issue number8
DOIs
StatePublished - Aug 29 2007

Fingerprint

Myostatin
myostatin
Muscle
Muscles
muscles
mice
follistatin
Follistatin
Transgenes
transgenes
Mothers
transforming growth factors
Mutation
Transforming Growth Factors
Growth
skeletal muscle
binding proteins
mechanism of action
Sheep
Carrier Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Quadrupling muscle mass in mice by targeting TGF-β signaling pathways. / Lee, Se Jin.

In: PLoS One, Vol. 2, No. 8, e789, 29.08.2007.

Research output: Contribution to journalArticle

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