| First Author | Schewe J | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5155 |
| PubMed ID | 31727896 | Mgi Jnum | J:282228 |
| Mgi Id | MGI:6378100 | Doi | 10.1038/s41467-019-13033-4 |
| Citation | Schewe J, et al. (2019) Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation. Nat Commun 10(1):5155 |
| abstractText | 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. |
