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

An intact renin-angiotensin system involving ANG II type 1 (AT₁) receptors is crucial for normal kidney development. It is still unclear in which cell types AT₁ receptor signaling is required for normal kidney development, maturation, and function. Because all kidney cells deriving from stroma progenitor cells express AT₁ receptors and because stromal cells fundamentally influence nephrogenesis and tubular maturation, we investigated the relevance of AT₁ 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 FoxD1-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 AT₁ receptors in renal stromal progenitors and their descendants does not disturb normal kidney development.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}