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 previousl y examined in adult transgenic mice. In adults, expression of human re nin was evident in kidney, reproductive tissues, adrenal gland and lun g. Previous studies of mouse and rat renin have demonstrated that kidn ey renin becomes evident at approximately 15 days of gestation and tha t expression is localized first to smooth muscle cells of the developi ng renal arterial tree and becomes progressively restricted to juxtagl omerular cells. As a prelude to performing cell specificity studies to elucidate the pattern of human renin gene expression in the developin g kidney, 15.5 and 17.5 days of gestation fetuses and newborns were ob tained for expression analysis. Tissues were pooled and expression was examined in kidney, liver, gastrointestinal (GI) tract, lung, heart a nd brain. The number of transgenic fetuses in each pool was determined by human renin-specific polymerase chain reaction of DNA purified fro m 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, extr emely high levels of human renin mRNA were detected in the newborn lun g. Expression of the human renin gene in these tissues was further con firmed by differential primer extension analysis which is capable of d ifferentiating the closely related human and mouse renin messages. The se transgenic mice should provide an interesting model to examine the expression and regulation of the human renin gene during kidney develo pment.