An efficient inducible model for the control of gene expression in renin cells

Abstract

ABSTRACTBackgroundFate mapping and genetic manipulation of renin cells have relied on either non-inducibleCrelines that can introduce developmental effects of gene deletion or BAC transgene-based inducible models that may be prone to spurious and/or ectopic gene expression.MethodsWe generated an inducible mouse model in whichCreERT2is under the control of the endogenousAkr1b7gene, an independent marker of renin cells.ResultsWe evaluated the pattern ofCreexpression inAkr1b7CreERT2/+;R26RmTmG/+mice in which Akr1b7+/renin+cells become GFP+ upon tamoxifen administration. At E18.5 and P5, GFP was found in Juxtaglomerular cells, along the arterioles, and in the glomerular mesangium. In adult kidneys, GFP was present mainly in Juxtaglomerular cells. In mice treated with captopril and a low sodium diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. In addition, we deleted renin in adult mice and found a marked reduction in kidney renin expression and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin+cells. Most importantly, mice with renin deletion induced in the adult developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin.ConclusionsRenin can be efficiently and specifically deleted in renin cells in adult life using our conditional model.Akr1b7CreERT2mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells.