Long term variations in growth hormone levels in sheep expressing an inserted gene for growth hormone

Abstract

Growth hormone (GH) affects important characteristics of animal production, including growth rate and fatness, so sheep transgenic for ovine GH have been produced to test their viability under field conditions. As the gene construct for ovine GH had a non-inducible metallothionein promoter, GH should be expressed uniformly and previous studies in an animal house have shown that secretion is nonpulsatile over a 10-hour period. However, when GH was measured over two years, the transgenic sheep were found to be subject to substantial changes (P< 0.001) in their plasma GH concentrations, with a particular rise in August. In two of the transgenic ewes, the GH levels stayed elevated, resulting in insulin-resistant diabetes and cachexia. We conclude that although the gene construct would be expected to secrete GH at a constant rate, plasma concentrations of GH in transgenic sheep were subject to significant long-term variations that may have had serious consequences for the animal.