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in juxtaglomerular cells
1 NIDDK, NIH, Bethesda, Maryland, United States
2 Pediatrics, University of Virginia, Charlottesville, Virginia, United States
3 Pediatrics and Biology, University of Virginia, Charlottesville, Virginia, United States
4 United States; NIDDK, NIH, Bethesda, Maryland, United States
* To whom correspondence should be addressed. E-mail: jurgens{at}intra.niddk.nih.gov.
By crossing mice with expression of Cre recombinase under control of the endogenous renin promoter (28) with mice in which exon 1 of the Gnas gene was flanked by loxP sites (4) we generated animals with preferential and near complete excision of Gs
in juxtaglomerular granular (JG) cells. Compared to wild type animals, mice with conditional Gs-deficiency had markedly reduced basal levels of renin expression and very low plasma renin concentrations. Furthermore, the acute release responses to furosemide, hydralazine, and isoproterenol were virtually abolished. Consistent with a state of primary renin depletion, Gs-deficient mice had a reduced arterial blood pressure, reduced levels of aldosterone, and low glomerular filtration rate. Renin content and renin secretion of JG cells in primary culture were drastically reduced, and the stimulatory response to the addition of PGE2 or isoproterenol was eliminated. Unexpectedly, Gs recombination was also observed in the renal medulla, and this was associated with a vasopressin-resistant concentrating defect. Our study shows that Cre recombinase under control of the renin promoter can be used for the excision of floxed targets from JG cells. We conclude that Gs-mediated signal transduction is essential and non-redundant in the control of renin synthesis and release.
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