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The avian skeletal
Volume 270,
Number 20,
Issue of May 19, pp. 12109-12116, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
-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 -actin gene directed high
level expression of human insulin-like growth factor I (IGF-I) in
stably transfected C
C myoblasts and transgenic
mice. Expression of the actin/IGF-I hybrid gene in
C
C 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
-actin-based vectors.
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