EXPRESSION OF THE HUMAN RENIN GENE IN TRANSGENIC MICE THROUGHOUT ONTOGENY

Expression of a human renin genomic DNA clone extending 900 base pairs upstream and 400 base pairs downstream of the gene has been previously examined in adult transgenic mice. In adults, expression of human renin was evident in kidney, reproductive tissues, adrenal gland and lung. Previous studies of mouse and rat renin have demonstrated that kidney renin becomes evident at approximately 15 days of gestation and that expression is localized first to smooth muscle cells of the developing renal arterial tree and becomes progressively restricted to juxtaglomerular cells. As a prelude to performing cell specificity studies to elucidate the pattern of human renin gene expression in the developing kidney, 15.5 and 17.5 days of gestation fetuses and newborns were obtained for expression analysis. Tissues were pooled and expression was examined in kidney, liver, gastrointestinal (GI) tract, lung, heart and brain. The number of transgenic fetuses in each pool was determined by human renin-specific polymerase chain reaction of DNA purified from placenta or tail biopsies. Renal human renin expression was abundant at all three time points. Expression was also evident in the GI tract at 15.5 and 17.5 days of gestation. Interestingly, although no human renin mRNA was evident in lung at 15.5 or 17.5 days of gestation, extremely high levels of human renin mRNA were detected in the newborn lung. Expression of the human renin gene in these tissues was further confirmed by differential primer extension analysis which is capable of differentiating the closely related human and mouse renin messages. These transgenic mice should provide an interesting model to examine the expression and regulation of the human renin gene during kidney development.