The nuclear receptor transcription factor Peroxisome Proliferator-Activated Receptor-gamma (PPARg) is an important regulator of renin gene expression. The PPARg-dependent stimulation of renin production could play essential role in the pathogenesis of arterial hypertension during obesity. The human renin gene has a unique PPARg binding sequence, the Pal3 site.

The aim of this study was to investigate the role of the Pal3 sequence in the regulation of the human renin gene in vivo.

We generated two transgenic mouse lines carrying the complete human renin gene with either the native Pal3 site (hPal3 line), or with inactivated Pal3 site (mPal3 line). The expression of human renin as well as the expression of the endogenous mouse renin which served as internal control was studied in hPal3 and mPal3 lines by immunohistochemistry and PCR.

As expected, human renin colocalized with the endogenous mouse renin in the renal juxtaglomerular (JG) cells of hPal3 mice. Human renin was expressed in some but not all cells positive for mouse renin in the kidneys of mPal3 mice. We also observed glomeruli with JG cells completely devoid of human renin, which still expressed mouse renin in the mPal3 strain. Thus, the mPal3 mice appear to produce less human renin than the hPal3 mice.

We conclude that the mutation of the human renin Pal3 sequence results in decreased human renin expression in transgenic mice. Our data strongly suggests that the Pal3 sequence is necessary for the cell-specific expression of the human renin gene in vivo.