ERYTHROID-SPECIFIC EXPRESSION OF HUMAN GROWTH-HORMONE AFFECTS BONE MORPHOLOGY IN TRANSGENIC MICE

The regulation of bone deposition and remodeling is highly complex. To further understand the influence of growth hormone on bone deposition , several lines of transgenic mice were generated that expressed the h uman growth hormone gene (hGH) driven by beta-globin regulatory elemen ts. In situ hybridization confirmed that the hGH gene in these mice wa s expressed in an erythroid tissue-specific manner; in the fetus hGH w as expressed in the liver and in the adult mice hGH was expressed in t he bone marrow, The bones of mice in two lines were visualized radiogr aphically by mammography, and relative bone densities were measured. T he transgenic mice had detectably more bone density than nontransgenic littermate controls by approximately 3 weeks of age and the relative difference in density increased with age, Histological cross-sections of the tibia showed that adult transgenic mice had increased average c ortical bone thickness when compared to their controls. The hypothesis is that the local effect of hGH release from differentiating erythroi d cells in the bone marrow is a major contributor to the increased bon e deposition in these transgenic mice.