TRANSGENIC MICE EXPRESSING CRE RECOMBINASE UNDER THE CONTROL OF THE HUMAN RENIN PROMOTER

Abstract

Loss-of-function animal models of the renin-angiotensin system are unanimously characterized by impaired urinary concentrating ability and progressive renal papillary atrophy. To track the activity of the human renin promoter during kidney development we generated transgenic mice expressing Cre recombinase driven by a 12.5 kb fragment of the human renin promoter. Detection of Cre by immunohistochemistry in the adult kidney revealed Cre expression in afferent arterioles, and to low degree in interlobular arteries. Cre mRNA was regulated in parallel with endogenous renin under various conditions (high, low salt diet, ACE inhibition, thirst, isoproterenol infusion) indicating the presence of key regulatory elements within the promoter. To address the activity of the human renin promoter during renal development we crossed the hRen-Cre line to the ROSA26-lacZ reporter strain. In the adult mouse we found lacZ staining in afferent arterioles and interlobular arteries overlapping with Cre protein expression. In addition, we detected intense lacZ staining in collecting ducts of the adult kidney where Cre expression was minimal, indicating Cre activity before adulthood. In the embryonic kidney lacZ staining was detected in the developing collecting duct including the branching tips of the collecting duct ampullae. Our data suggest that besides its well known activity in renal vessels the human renin promoter is active in the collecting duct system during kidney development proposing functional relevance of renin expression for normal kidney development.