This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hubert, C. Articles by Corvol, P. Search for Related Content PubMed PubMed Citation Articles by Hubert, C. Articles by Corvol, P.

Effects of Mineralocorticoid Receptor Gene Disruption on the Components of the Renin-Angiotensin System in 8-Day-Old Mice

INSERM U36-Laboratoire de Médecine Expérimentale (C.H., J.M.G., P.C.) Collège de France Paris, France 75005
Division Molecular Biology of the Cell I (S.B., G.S.) German Cancer Research Center Heidelberg, Germany

Targeted disruption of mineralocorticoid receptor (MR) gene results in pseudohypoaldosteronism type I with failure to thrive, severe dehydration, hyperkalemia, hyponatremia, and high plasma levels of renin, angiotensin II, and aldosterone. In this study, mRNA expression of the different components of the renin-angiotensin system (RAS) were evaluated in liver, lung, heart, kidney and adrenal gland to assess their response to a state of extreme sodium depletion. Angiotensinogen, renin, angiotensin-I converting enzyme, and angiotensin II receptor (AT₁ and AT₂) mRNA expressions were determined by Northern blot and RT-PCR analysis. Furthermore, in situ hybridization and immunohistochemistry allowed us to identify the cell types involved in the variation of the RAS component expression. In the heterozygous mice (MR+/-), compared with wild-type mice (MR+/+), there was no significant variation of any mRNA of the RAS components. In MR knockout mice (MR-/-), compared with wild-type mice, there were significant increases in the expression level of several RAS components. In the liver, angiotensinogen and AT₁ receptor mRNA expressions were moderately stimulated. In the kidney, renin mRNA was increased up to 10-fold and in situ hybridization showed a marked recruitment of renin-producing cells; however, the levels of angiotensin-I converting enzyme mRNA and AT₁ mRNA were not changed. Interestingly, in adrenal gland, renin expression was also strongly up-regulated in a thickened zona glomerulosa, whereas AT₁ mRNA expression remained unchanged. Altogether, these results demonstrate that in the MR knockout mice model, RAS component expressions are differentially altered, renin being the most stimulated component. Angiotensinogen and AT₁ in the liver are also increased, but the other elements of the RAS are not affected.

This article has been cited by other articles:

				L. Kurtz, F. Schweda, C. de Wit, W. Kriz, R. Witzgall, R. Warth, A. Sauter, A. Kurtz, and C. Wagner Lack of Connexin 40 Causes Displacement of Renin-Producing Cells from Afferent Arterioles to the Extraglomerular Mesangium J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1103 - 1111. [Abstract] [Full Text] [PDF]

				N. Makhanova, M. L.S. Sequeira-Lopez, R. A. Gomez, H.-S. Kim, and O. Smithies Disturbed Homeostasis in Sodium-Restricted Mice Heterozygous and Homozygous for Aldosterone Synthase Gene Disruption Hypertension, December 1, 2006; 48(6): 1151 - 1159. [Abstract] [Full Text] [PDF]

				M. Lacoste, Y. Cai, L. Guicharnaud, F. Mounier, Y. Dumez, R. Bouvier, F. Dijoud, M. Gonzales, J. Chatten, A.-L. Delezoide, et al. Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios: Role of the Renin-Angiotensin System J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2253 - 2263. [Abstract] [Full Text] [PDF]

				L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]

				Y. Yang, Y. Cui, W. Wang, L. Zhang, L. Bufford, S. Sasaki, Z. Fan, and H. Nishimura Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2004; 287(4): R915 - R924. [Abstract] [Full Text] [PDF]

				H. Nishimura, Y. Yang, C. Hubert, J.-M. Gasc, K. Ruijtenbeek, J. De Mey, H. A. J. S. Boudier, and P. Corvol Maturation-dependent changes of angiotensin receptor expression in fowl Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R231 - R242. [Abstract] [Full Text] [PDF]

				P. C. White Aldosterone: Direct Effects on and Production by the Heart J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2376 - 2383. [Full Text] [PDF]

				H. Okada, T. Inoue, Y. Kanno, T. Kobayashi, Y. Watanabe, J. B. Kopp, R. M. Carey, and H. Suzuki Interstitial Fibroblast-Like Cells Express Renin-Angiotensin System Components in a Fibrosing Murine Kidney Am. J. Pathol., March 1, 2002; 160(3): 765 - 772. [Abstract] [Full Text] [PDF]

				D. Le Menuet, R. Isnard, M. Bichara, S. Viengchareun, M. Muffat-Joly, F. Walker, M.-C. Zennaro, and M. Lombes Alteration of Cardiac and Renal Functions in Transgenic Mice Overexpressing Human Mineralocorticoid Receptor J. Biol. Chem., October 12, 2001; 276(42): 38911 - 38920. [Abstract] [Full Text] [PDF]