Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/23195
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Type: Journal article
Title: Rskα-actin/hIGF-1 transgenic mice with increased IGF-I in skeletal muscle and blood: Impact on regeneration, denervation and muscular dystrophy
Other Titles: Rsk alpha-actin/hIGF-1 transgenic mice with increased IGF-I in skeletal muscle and blood: Impact on regeneration, denervation and muscular dystrophy
Author: Shavlakadze, T.
Boswell, J.
Burt, D.
Asante, E.
Tomas, F.
Davies, M.
White, J.
Grounds, M.
Goddard, C.
Citation: Growth Hormone & IGF Research, 2006; 16(3):157-173
Publisher: Churchill Livingstone
Issue Date: 2006
ISSN: 1096-6374
1532-2238
Statement of
Responsibility: 
T. Shavlakadze, J.M. Boswell, D.W. Burt, E.A. Asante, F.M. Tomas, M.J. Davies, J.D. White, M.D. Grounds, C. Goddard
Abstract: Human IGF-I was over-expressed in skeletal muscles of C57/BL6xCBA mice under the control of the rat skeletal alpha-actin gene promoter. RT-PCR verified expression of the transgene in skeletal muscle but not in the liver of 1- and 21-day old heterozygote transgenic mice. The concentration of endogenous mouse IGF-I, measured by an immunoassay which does not detect human IGF-I, was not significantly different between transgenic mice and wild-type littermates (9.5 +/- 0.8 and 13.3 +/- 1.9 ng/g in muscle; 158.3 +/- 18.6 and 132.9 +/- 33.1 ng/ml in plasma, respectively). In contrast, quantitation with antibodies to human IGF-I showed an increase in IGF-I of about 100 ng/ml in plasma and 150 ng/g in muscle of transgenic mice at 6 months of age. Transgenic males, compared to their age matched wild-type littermates, had a significantly higher body weight (38.6 +/- 0.53 g vs. 35.8 +/- 0.64 g at 6 months of age; P < 0.001), dry fat-free carcass mass (5.51 +/- 0.085 vs. 5.08 +/- 0.092 g; P < 0.001) and myofibrillar protein mass (1.62 +/- 0.045 vs. 1.49 +/- 0.048 g; P < 0.05), although the fractional content of fat in the carcass was lower (167 +/- 7.0 vs. 197 +/- 7.7 g/kg wet weight) in transgenic animals. There was no evidence of muscle hypertrophy and no change in the proportion of slow type I myofibres in the limb muscles of Rskalpha-actin/hIGF-I transgenic mice at 3 or 6 months of age. Phenotypic changes in Rskalpha-actin/hIGF-I mice are likely to be due to systemic as well as autocrine/paracrine effects of overproduction of IGF-I due to expression of the human IGF-I transgene. The effect of muscle specific over-expression of Rskalpha-actin/hIGF-I transgene was tested on: (i) muscle regeneration in auto-transplanted whole muscle grafts; (ii) myofibre atrophy following sciatic nerve transection; and (iii) sarolemmal damage and myofibre necrosis in dystrophic mdx muscle. No beneficial effect of muscle specific over-expression of Rskalpha-actin/hIGF-I transgene was seen in these three experimental models.
Keywords: IGF-1; Transgenic mice; skeletal muscle; circulating IGF-1; growth; regeneration; atrophy; mdx
Rights: © 2006, Elsevier
RMID: 0020061361
DOI: 10.1016/j.ghir.2005.11.003
Appears in Collections:Obstetrics and Gynaecology publications

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