This Article Full Text Full Text (PDF) 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, G. Articles by Kim, H.-S. Search for Related Content PubMed PubMed Citation Articles by Lee, G. Articles by Kim, H.-S.

Homeostatic Responses in the Adrenal Cortex to the Absence of Aldosterone in Mice

Departments of Pathology and Lab Medicine (G.L., N.M., K.C., O.S., H.-S.K.) and Cellular and Molecular Physiology (K.C.), University of North Carolina, Chapel Hill, North Carolina 27599-7525; Department of Pediatrics (M.L.S.L., R.A.G.), University of Virginia, Charlottesville, Virginia 22908; Department of Oral Biochemistry College of Dentistry (G.L.), Seoul National University, Seoul 110-749, South Korea; and Institute of Cytology and Genetics (N.M.), Siberian Division, Russian Academy of Sciences, Novosibirsk 630090, Russia

Address all correspondence and requests for reprints to: Hyung-Suk Kim, Ph.D., Department of Pathology and Laboratory Medicine, University of North Carolina, 703 Brinkhous-Bullitt Building, Chapel Hill, North Carolina 27599-7525. E-mail: hskim{at}med.unc.edu.

To study the effects of decreased amounts or absence of aldosterone on development and endocrine function, we have disrupted the mouse gene, Cyp11b2, coding for aldosterone synthase (AS) by replacing its first two exons with sequences coding for enhanced green fluorescent protein. The null pups fail to thrive postnatally, and about 30% die between d 7 and 28. Aldosterone in plasma and AS mRNA in adrenal glands are undetectable in the null mice. Adult AS-null mice are small, weigh 75% of wild type, are hypotensive, have increased concentrations of plasma K⁺ and corticosterone, and a decreased concentration of plasma Cl^–. Their plasma renin and angiotensin II concentrations are 45x and 4x wild type. The adrenal cortex is disorganized and has cells that contain marked accumulations of lipid. The zona glomerulosa is widened and includes easily detectable renin-containing cells, not seen in the wild-type adrenal gland. In the AS–/– adrenals, the level of mRNA for Cyp11b1, coding for 11ß-hydroxylase, is 150% wild type. The adrenal glands of the null mice consequently show evidence of a greatly activated renin-angiotensin system and up-regulation of glucocorticoid production. In the AS-null mice enhanced green fluorescent protein fluorescence is mainly at the boundary between the cortex and medulla, where apoptotic cells are numerous. These data are consistent with the absence of aldosterone in the AS-null mice inducing an increased cell-turnover of cells in the adrenals that normally become AS expressing and their migration to the medullary boundary where they apoptose.

This article has been cited by other articles:

				J. M. Luther, Z. Wang, J. Ma, N. Makhanova, H.-S. Kim, and N. J. Brown Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta Endocrinology, May 1, 2009; 150(5): 2229 - 2236. [Abstract] [Full Text] [PDF]

				J Manolopoulou, M Bielohuby, S J Caton, C E Gomez-Sanchez, I Renner-Mueller, E Wolf, U D Lichtenauer, F Beuschlein, A Hoeflich, and M Bidlingmaier A highly sensitive immunofluorometric assay for the measurement of aldosterone in small sample volumes: validation in mouse serum J. Endocrinol., February 1, 2008; 196(2): 215 - 224. [Abstract] [Full Text] [PDF]

				M. Kawamura, H. Itoh, S. Yura, H. Mogami, S.-I. Suga, H. Makino, Y. Miyamoto, Y. Yoshimasa, N. Sagawa, and S. Fujii Undernutrition in Utero Augments Systolic Blood Pressure and Cardiac Remodeling in Adult Mouse Offspring: Possible Involvement of Local Cardiac Angiotensin System in Developmental Origins of Cardiovascular Disease Endocrinology, March 1, 2007; 148(3): 1218 - 1225. [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]

				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]

				N. Makhanova, G. Lee, N. Takahashi, M. L. Sequeira Lopez, R. A. Gomez, H.-S. Kim, and O. Smithies Kidney function in mice lacking aldosterone Am J Physiol Renal Physiol, January 1, 2006; 290(1): F61 - F69. [Abstract] [Full Text] [PDF]