Expression of insulin-like growth factor-I in skeletal muscle of transgenic swine

Although growth hormone is considered the primary growth-promoting hormone in mammals, many of its effects are thought to be mediated by insulin-like growth factor-I (ICF-I), which is a potent mitogen that stimulates cell pro liferation and synthesis of DNA and protein. The aim of this research was t o determine whether directing expression of IGF-l specifically to striated muscle would enhance lean muscle growth in swine. Transgenic pigs were prod uced by microinjection of zygotes with a fusion gene consisting of the regu latory sequences of an avian skeletal a-actin gene and a cDNA encoding huma n IGF-I. All but one of 13 transgenic pigs expressed the ICF-I transgene. M uscle IGF-I concentrations varied from 20 to 1702 ng g(-1) muscle in transg enic pigs compared with less than 10 ng g(-1) muscle in control pigs. Muscl e ICF-I concentrations were in general agreement with abundance of IGF-I mR NA on Northern blots. Serum IGF-I concentrations in transgenic pigs (160 +/ - 6.8 ng ml(-1)) did not differ from that of littermate control pigs (143 /- 6.5 ng ml(-1)). Daily weight gain from 20 to 60 kg body weight was simil ar for transgenic and littermate control pigs (865 +/- 29.6 g vs. 876 +/- 1 8.9 g day(-1)). Body composition of eight transgenic and eight control pigs was estimated by X-ray absorptiometry (DXA) scanning at 60 kg body weight. The DXA results indicated transgenic female pigs had significantly less fa t and more lean tissue than female littermate controls (P < 0.05 for each). However, body composition of transgenic and control boars did not differ. Subsequently nine of ten founders transmitted their transgene to G1 progeny , which will be used for evaluation of growth rate, feed efficiency and car cass composition. Transgenic and control pigs did not differ in general app earance, and no gross abnormalities, pathologies or health-related problems were encountered. Based on these results we conclude that enhancing IGF-I specifically in skeletal muscle may have a positive effect on carcass compo sition of swine.