Table 2.
Mouse Models of Hyperaldosteronism
| Mouse Model | Description | Phenotype | Reference |
|---|---|---|---|
| Kcnk3−/− | K+ channel 2 pore domain, member 3 (Task1) deletion | Elevated plasma aldosterone relative to suppressed plasma renin; aberrant Cyp11b1 expression in zF in females and in prepubertal males; decreased plasma K+; elevated aldosterone and high blood pressure remediable by dexamethasone | Heitzmann, et al. (26) |
| Kcnk3−/−/Dkk3−/− | Task1 and Dickkopf WNT signaling pathway inhibitor 3 deletion | Increased expression Cyp11b2; hyperaldosteronism phenotype extended to adult males | El Wakil, et al. (27) |
| Kcnk3−/−/Kcnk9−/− | Task1 and -3 deletion | Elevated plasma aldosterone relative to suppressed plasma renin; elevated aldosterone not suppressible by high salt diet; hyperaldosteronism phenotype extended to adult males | Davies, et al. (28) |
| Kcnk9−/− | K+ channel 2 pore domain, member 9 (Task3) deletion | Mild overproduction of aldosterone relative to suppressed plasma renin; aldosterone not suppressible by high salt diet; salt-sensitive high blood pressure | Guagliardo, et al. (29) |
| Penton, et al. (30) | |||
| Kcnmb1−/− | K+ channel, Ca2+-activated, subunit β deletion | Elevated plasma aldosterone, high blood pressure, renal K+ retention | Grimm, et al. (31) |
| Kcnma1−/− | K+ channel, Ca2+-activated, subunit α deletion | Elevated plasma aldosterone, high blood pressure, decreased plasma K+, increased vascular tone | Sausbier, et al. (32) |
| ΔCat | Constitutive activation of β catenin in adrenal cortex | Elevated plasma aldosterone; adrenal hyperplasia; development of adrenal carcinoma | Berthon, et al. (33) |
| ApcMin/+ | Expression of a truncated form of tumor suppressor protein Apc | Elevated plasma aldosterone and corticosterone; elevated plasma volume and high blood pressure | Bhandaru, et al. (34) |
| Cry1−/−/Cry2−/− | Deletion of core components of circadian clock (Cry1 and Cry2) | Elevated plasma aldosterone; salt-sensitive high blood pressure; increased expression of Hsd3b6 | Doi, et al. (35) |
| Tgfb1L/L | Reduced expression (≈10% normal) of Tgfb1 mRNA | Increased aldosterone-to-renin ratio (6× normal), elevated blood pressure; decreased urinary water and electrolyte output | Kakoki, et al. (36) |
| Enu | Random mutagenesis screen using N-ethyl-N-nitrosourea | Increased aldosterone-to-renin ratio; increased Cyp11b2 gene expression | Spyroglou, et al. (37) |
| Cyp11b2 hi/hi | Substitution of unstable 3′UTR of Cyp11b2 with more stable 3′UTR of bovine GH | Modest increase in Cyp11b2 expression; salt-sensitive high blood pressure | Makhanova (38) |
| hAS+/− | Human CYP11B1 promoter fused to coding region of human CYP11B2 | Elevated plasma aldosterone; salt-sensitive high blood pressure; increased CYP11B2 gene expression | Gu, et al. (39) |
Abbreviations: 3′UTR, untranslated region; Apc, adenomatous polyposis coli gene; Cry1, cryptochrome-1 gene; Cry2, cryptochrome-2 gene; Dkk3, dickkopf family gene; Enu, N-ethyl-N-nitrosourea; GH, growth hormone; hAS, human aldosterone synthase; Hsd3b6, gene encoding 3β- and steroid δ-isomerase 6 (hydroxy-δ-5-steroid dehydrogenase); Tgfb1, transforming growth factor β1; ΔCat, constitutively activated β-catenin.