Administration of a mutated myostatin propeptide to neonatal mice significantly enhances skeletal muscle growth

Mol Reprod Dev. 2010 Jan;77(1):76-82. doi: 10.1002/mrd.21111.

Abstract

Myostatin is a dominant inhibitor of skeletal muscle development and growth. As transgenic over-expression of myostatin propeptide dramatically enhanced muscle mass, we hypothesized that administration of myostatin propeptide will increase muscle growth. In this study, the wild-type form of porcine myostatin propeptide and its mutated form at the cleavage site of metalloproteinases of BMP-1/TLD family were produced from insect cells. In vitro A204 cells reporter assays showed that both wild-type and the mutated propeptides depressed myostatin activity. The recombinant propeptides at four-fold myostatin concentration can effectively block myostatin function during co-incubation with A204 cells. In particular, the mutated propeptide appeared much more effective than wild-type propeptide over a long period during the in vitro co-incubation. Administration of the mutated propeptide to neonatal mice at the age of 11 and 18 days was tested and showed significant increase in growth performance by 11-15% from the age of 25 to 57 days (P < 0.05). The major skeletal muscles of mice that were injected with mutated propeptide were 13.5-24.8% heavier than the control group (P < 0.05) as a result of muscle fiber hypertrophy. In conclusion, administration of the mutated myostatin propeptide during the neonatal period is an effective way for promoting muscle growth.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Line
  • Female
  • Humans
  • Insecta
  • Male
  • Mice
  • Muscle, Skeletal* / anatomy & histology
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / growth & development
  • Mutation*
  • Myostatin* / genetics
  • Myostatin* / pharmacology
  • Protein Precursors / genetics
  • Protein Precursors / pharmacology
  • Swine

Substances

  • Myostatin
  • Protein Precursors