Human IGF-I was over-expressed in skeletal muscles of C57/BL6 x CBA 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-L 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 Rskot-actin/hIGF-I transgenic mice at 3 or 6 months of age. Phenotypic changes in Rskot-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 Rskot-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 Rsk alpha-actin/hIGF-I transgene was seen in these three experimental models. (c) 2006 Elseiver Ltd. All rights reserved.
Shavlakadze, T., Boswell, J. M., Burt, D. W., Asante, E. A., Tomas, F. M., Davies, M. J., ... Goddard, C. (2006). Rskα-actin/hIGF-1 transgenic mice with increased IGF-I in skeletal muscle and blood: Impact on regeneration, denervation and muscular dystrophy. Growth Hormone & IGF Research, 16(3), 157-173. https://doi.org/10.1016/j.ghir.2005.11.003