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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: |
Schewe, J., Seidel, E.  ORCID: https://orcid.org/0000-0003-3334-3950, Forslund, S. ORCID: https://orcid.org/0000-0003-4285-6993, Marko, L. ORCID: https://orcid.org/0000-0003-1888-5575, Peters, J., Muller, D.N. ORCID: https://orcid.org/0000-0003-3650-5644, Fahlke, C., Stölting, G. ORCID: https://orcid.org/0000-0002-2339-0545 and Scholl, U. ORCID: https://orcid.org/0000-0002-0309-8045
|
| 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 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 10 |
| Number: | 1 |
| 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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