JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter

In the kidney, renin gene expression is exquisitely localized to the juxtag lomerular (JG) cells lining the afferent arteriole, having the capacity to regulate renin synthesis in response to a variety of physiological cues. We investigated human renin gene expression in transgenic mice containing a g enomic construct driven by 149 bp of its proximal promoter to elucidate whe ther this was sufficient to confer JG-specific expression. Whereas human re nin mRNA was permissively expressed in most tissues, the transgene was expr essed mainly in JG cells in the kidney. Active human renin and human proren in were found in the systemic circulation at levels consistent with previou s transgenic models. Remarkably, two lines displayed an appropriate upregul ation of transgene mRNA in response to angiotensin-converting enzyme inhibi tion, and two lines exhibited a downregulation of transgene mRNA in respons e to subpressor and presser doses of ANG II. Our results suggest that 149 b p of the human renin proximal promoter, in a context of a genomic construct , are sufficient to confer human renin expression in renal JG cells and at least some aspects of appropriate regulation.