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Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation

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Item Type:Article
Title:Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation
Creators Name:Schewe, J. and Seidel, E. and Forslund, S. and Marko, L. and Peters, J. and Muller, D.N. and Fahlke, C. and Stölting, G. and Scholl, U.
Abstract:Gain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2(R180Q/+) mice, adrenal morphology is normal, but Cyp11b2 expression and plasma aldosterone levels are elevated. Male Clcn2(R180Q/+) mice have increased aldosterone:renin ratios as well as elevated blood pressure levels. The counterpart knockout model (Clcn2(-/-)), in contrast, requires elevated renin levels to maintain normal aldosterone levels. Adrenal slices of Clcn2(R180Q/+) mice show increased calcium oscillatory activity. Together, our work provides a knockin mouse model with a mild form of primary aldosteronism, likely due to increased chloride efflux and depolarization. We demonstrate a role of ClC-2 in normal aldosterone production beyond the observed pathophysiology.
Keywords:Adrenal Glands, Aldosterone, Amino Acid Sequence, Animal Disease Models, Base Sequence, Blood Pressure, Chloride Channels, Chlorides, Cytochrome P-450 CYP11B2, Heterozygote, Hyperaldosteronism, Inbred C57BL Mice, Mutation, Phenotype, Renin, Sodium, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5155
Date:14 November 2019
Additional Information:Erratum in: Nat Commun 13(1):3066.
Official Publication:https://doi.org/10.1038/s41467-019-13033-4
PubMed:View item in PubMed

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