title: Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsalpha in juxtaglomerular cells.
abstract: By crossing mice with expression of Cre recombinase under control of the endogenous renin promoter (Sequeira Lopez ML, Pentz ES, Nomasa T, Smithies O, Gomez RA. Dev Cell 6: 719-728, 2004) with mice in which exon 1 of the Gnas gene was flanked by loxP sites (Chen M, Gavrilova O, Liu J, Xie T, Deng C, Nguyen AT, Nackers LM, Lorenzo J, Shen L, Weinstein LS. Proc Natl Acad Sci USA), we generated animals with preferential and nearly complete excision of Gsalpha in juxtaglomerular granular (JG) cells. Compared with wild-type animals, mice with conditional Gsalpha 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, Gsalpha-deficient mice had reduced arterial blood pressure, reduced levels of aldosterone, and a 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 PGE(2) or isoproterenol was eliminated. Unexpectedly, Gsalpha 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 Gsalpha-mediated signal transduction is essential and nonredundant in the control of renin synthesis and release.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1370, USA.
authors.forename: Limeng
authors.initials: L
authors.lastname: Chen
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Mona
authors.initials: M
authors.lastname: Oppermann
authors.forename: Robert
authors.initials: R
authors.lastname: Faulhaber-Walter
authors.forename: Yuning
authors.initials: Y
authors.lastname: Huang
authors.forename: Diane
authors.initials: D
authors.lastname: Mizel
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Maria Luisa Sequeira
authors.initials: ML
authors.lastname: Lopez
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
authors.forename: Josie P
authors.initials: JP
authors.lastname: Briggs
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000652:urine; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D006830:Hydralazine / Q000494:pharmacology; D019426:Integrases / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration; D011994:Recombinant Proteins / Q000494:pharmacology; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D004232:Diuretics; D011994:Recombinant Proteins; D006830:Hydralazine; D000450:Aldosterone; D005665:Furosemide; D051546:Cyclooxygenase 2; C045073:Cre recombinase; D019426:Integrases; D012083:Renin; D019205:GTP-Binding Protein alpha Subunits, Gs; D015232:Dinoprostone; D007545:Isoproterenol