Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice

J Biol Chem. 1995 May 19;270(20):12109-16. doi: 10.1074/jbc.270.20.12109.


The avian skeletal alpha-actin gene was used as a template for construction of a myogenic expression vector that was utilized to direct expression of a human IGF-I cDNA in cultured muscle cells and in striated muscle of transgenic mice. The proximal promoter region, together with the first intron and 1.8 kilobases of 3'-noncoding flanking sequence of the avian skeletal alpha-actin gene directed high level expression of human insulin-like growth factor I (IGF-I) in stably transfected C2C12 myoblasts and transgenic mice. Expression of the actin/IGF-I hybrid gene in C2C12 muscle cells increased levels of myogenic basic helix-loop-helix factor and contractile protein mRNAs and enhanced myotube formation. Expression of the actin/IGF-I hybrid gene in mice elevated IGF-I concentrations in skeletal muscle 47-fold resulting in myofiber hypertrophy. IGF-I concentrations in serum and body weight were not increased by transgene expression, suggesting that the effects of transgene expression were localized. These results indicate that sustained overexpression of IGF-I in skeletal muscle elicits myofiber hypertrophy and provides the basis for manipulation of muscle physiology utilizing skeletal alpha-actin-based vectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / genetics*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Fusion
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • Genes, Synthetic
  • Genetic Vectors*
  • Helix-Loop-Helix Motifs
  • Hypertrophy
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics
  • Muscles / cytology*
  • Organ Specificity
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / biosynthesis*
  • Transfection


  • Actins
  • Muscle Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Insulin-Like Growth Factor I