Apparently normal kidney development in mice with conditional disruption of ANGII-AT1 receptor genes in FoxD1 positive stroma cell precursors.

An intact renin-angiotensin system involving ANG II type 1 (AT(1)) receptors is crucial for normal kidney development. It is still unclear in which cell types AT(1) receptor signaling is required for normal kidney development, maturation, and function. Because all kidney cells deriving from stroma progenitor cells express AT 1 receptors and because stromal cells fundamentally influence nephrogenesis and tubular maturation, we investigated the relevance of AT(1) receptors in stromal progenitors and their descendants for renal development and function. For this aim, we generated and analyzed mice with conditional deletion of AT(1A )receptor in the FoxD1 cell lineage in combination with global disruption of the AT(1B) receptor gene. These FoxD1-AT1ko mice developed normally. Their kidneys showed neither structural nor functional abnormalities compared with wild-type mice, whereas in isolated perfused FoxDl-AT1ko kidneys, the vasoconstrictor and renin inhibitory effects of ANG II were absent. In vivo, however, plasma renin concentration and renal renin expression were normal in FoxD1-AT1ko mice, as were blood pressure and glomerular filtration rate. These findings suggest that a strong reduction of AT(1) receptors in renal stromal progenitors and their descendants does not disturb normal kidney development.