Figure 9.

Model for impairment and restoration of Na⁺ balance and BP in Af17^−/− mice. Under basal conditions such as the normal Na⁺ diet, deletion of Af17 leads to significantly increased H3 K79 methylation, and subsequently impaired ENaC activity, disturbance of Na⁺ balance, and decreased BP. The mildly increased plasma [aldo] is not sufficient to antagonize the effect of Af17 loss on H3 K79 methylation and thus fails to rescue the Af17^−/− phenotype. Under aldo excess such as aldo perfusion or the low Na⁺ diet dramatically increased aldo levels efficiently decrease H3 K79 methylation regardless of the presence or absence of Af17, leading to comparable levels of H3 K79 methylation and a renal physiology and BP phenotype indistinguishable between Af17^+/+ and Af17^−/− mice. For clarity, detailed mechanisms by which Af17²³ and aldo²² inhibit H3 K79 methylation are not shown. The dotted line indicates unknown mechanisms.