Growth Hormone Overproduction in Transgenic Mice: Phenotypic Alterations and Deduced Animal Models

Abstract

Transgenic mice play a key role in biomedical research since they can be designed to be optimum animal models for studying specific scientific problems. In the early 1980s, transfer of growth hormone (GH) fusion genes to the germ-line of mice demonstrated that foreign genetic information may be stably integrated and expressed to yield a biologically active product, as evidenced by markedly stimulated growth of these mice. Consequently, GH structural genes have been used as welcome reporters for functional analyses of regulatory DNA sequences. Phenotypic characterisation of mice expressing various GH fusion genes revealed a typical spectrum of alterations. These alterations included an increased growth of body, skeleton, muscles, and internal organs; endocrine and metabolic changes; as well as pathological alterations primarily of liver and kidneys. From these alterations, which occur reproducibly in an age-dependent manner, animal models have been developed for studying the long-term effects of elevated GH, the pathogenesis of glomerulosclerosis and the mechanisms involved in hepatocarcinogenesis. In this review, we compare GH transgenic mice with the classical animal models which have been used for studying these problems with respect to both the scientific quality of these models and the animal welfare aspect. The well-being of GH transgenic mice may — at least if young animals are investigated — be less disturbed than that of the comparable animal models produced conventionally. The scientific questions currently investigated using GH transgenic mice appear to be sufficiently important for mankind to be justified on ethical criteria.