Insertion, expression and physiology of growth-regulating genes in ruminants.

Transgenic sheep with elevated concentrations of circulating growth hormone (GH) were produced by microinjecting recombinant DNA into pronuclei of zygotes. The transgenes were fusion genes of non-GH promoters with coding sequences of various growth hormone genes including human, ovine or bovine. In addition, sheep transgenic with the human growth hormone releasing factor gene were produced. Non-GH promoters for fusion genes allowed novel regulation of GH production in ectopic tissues, including the kidney, liver and gut. Elevated levels of GH profoundly altered plasma IGF-1 without significantly altering rate of growth or feed efficiency. Carcass composition was altered with reduced fat. Elevated GH induced diabetes, resulting in death by 1 year of age. These studies indicate the need for improved regulation of inserted genes or investigation of alternative systems, such as GH receptors, to improve growth using the transgenic approach in ruminants.