Table 2.
Comparison of the different adrenal phenotypes of Task1 −/− [55], Task1 −/−/Task3 −/− double knockout [28, 50], Task3 −/− [51, 103], and Task1 −/−/Dkk3 −/− double knockout mice [34]
| Parameter | Task1−/− ♀+♂ [55] | Task1 −/−/Task3 −/− ♂ [28, 50]} | Task3−/− ♀+♂ [103] | Task3−/− ♂ [51] | Newborn Task3 −/− [7] | Task1 −/−/Dkk3 −/− ♀+♂ [34] |
|---|---|---|---|---|---|---|
| Membrane potential of adrenocortical cells under control conditions (compared to wild-type cells; only cells from male mice were analyzed) | Depolarized primary cultured cells | Depolarized glomerulosa cells in adrenal slices | Depolarized primary cultured cells | Glomerulosa cells in adrenal slices were not depolarized | n.a. | Depolarized primary cultured cells; no difference between Task1 −/− and Task1 −/−/Dkk3 −/− cells |
| Cytosolic Ca2+ | n.a. | n.a. | Spontaneous oscillations in glomerulosa cells (adrenal slices) under control, which were silenced by Ang-II; smaller increase under high K+ | n.a. | n.a. | n.a. |
| Aldosterone | Severe hyperaldosteronism in female mice was independent of the salt intake, but normalized by dexamethasone; male mice were normal | Under control conditions hyperaldosteronism in male mice in one study [50]; no hyperaldosteronism in another study [28]; no suppression (even an increase) under high Na+ and normal increase under low Na+ [28] | Normal aldosterone under control; no suppression under high Na+, smaller decrease under low K+ in female mice, and normal increase under high K+ and low Na+; increased aldosterone secretion in perifused adrenal glands (with absent Ang-II) | Mild hyperaldosteronism under control; no suppression under high Na+, normal increase under high K+ and low Na+; higher in vivo Ang-II-dependent aldosterone secretion | Severe hyperaldosteronism; additional increase of corticosterone and progesterone | Hyperaldosteronism in male Task1 −/−/Dkk3 −/− mice, while male Task1-/- had normal aldosterone levels; no further increase by high K+ |
| Renin | Decreased plasma renin in female mice under control condition, but not in male mice | Decreased plasma renin in male mice under control [50] or no change [28], low Na+, and under high Na+ [28] | Decreased plasma renin under control and under high Na+; increase under low Na+ similar in both genotypes | Decreased plasma renin under control, low Na+, and under high Na+ | Normal plasma renin, but decreased renin in renal lysates; abnormal adrenal renin production | Decreased plasma renin levels in Task1 −/−/Dkk3 −/− mice of both sexes |
| Aldosterone/renin ratio (ARR) | Increased in female mice | Increased | Increased | Increased | Increased | Increased in male Task1 −/−/Dkk3 −/− mice, while male Task1 −/− had normal ARR |
| Blood pressure (SBP: systolic blood pressure, DBP: diastolic blood pressure) | SBP increased in female mice, but not in male mice; canrenoate normalized SBP | n.a. | SBP was normal under control but increased under high Na+ | SBP and DBP increased under control; candesartan normalized DBP; SBP increased under high Na+ | n.a. | n.a. |
| Cyp11b2 (aldosterone synthase) expression | Increased Cyp11b2 mRNA and protein in female mice under control; no further increase of protein under high K+ | n.a. | Cyp11b2 mRNA not altered under control | Increased Cyp11b2 mRNA under control and high Na+, protein levels were not increased | Increased Cyp11b2 mRNA in newborn mice, but not in 12-day-old mice | Increased Cyp11b2 mRNA in male Task1 −/−/Dkk3 −/− mice, but normal levels in male Task1 −/− mice |
| Aldosterone synthase localization (“zonation”) | Female mice: ectopic expression in zona fasciculata, suppressed expression in zona glomerulosa; normal zonation in male mice | Normal zonation in male mice with glomerulosa-specific expression | Normal zonation in male and female mice with glomerulosa-specific expression | Normal zonation in male mice with glomerulosa-specific expression | Normal zonation with glomerulosa-specific expression | Normal zonation with glomerulosa-specific expression in male Task1 −/−/Dkk3 −/− mice |
| Plasma electrolytes | Hypokalemia in female mice, normal plasma Na+ | Hypokalemia | No difference in plasma K+ and Na+ | Hypokalemia | Hypernatremia in 4-day-old mice | n.a. |
| Additional data | Increased amiloride-sensitive current in distal colon of female mice | – | Sex-dependent Task3 expression in wt mice (♂: higher than ♀ ZG+ZF; ♀: ZG) | Decreased heart rate at night | Increased expression of Hsd3b6 | No effect of Dkk3 knockout in ♀ Task1 −/− |
Please note, that the phenotype of Task3 −/− mice was analyzed by two different groups using independent Task3 −/− models. The phenotype of Task1 −/−/Task3 −/− mice and of one of the Task3 −/− strains [51] was only analyzed in male mice. Aldosterone levels were measured in plasma or in 24 h urine samples. If not stated otherwise, the phenotype of knockout mice is compared with the one of wild-type mice
n.a. not analyzed, ZG zona glomerulosa, ZF zona fasciculata