59Fe-distribution in conditional ferritin-H-deleted mice

The objective was to explore how ferritin-H deletion influences (59)Fe-distribution and excretion-kinetics in mice. Kinetics of (59)Fe-release from organs, whole-body excretion, and distribution-kinetics of intravenously injected (59)Fe trace amounts were compared in iron-deficient and iron-replete mice with (Fth(Δ/Δ)) and without (Fth(lox/lox)) conditional Mx-Cre-induced ferritin-H deletion. (59)Fe was released from spleen and liver beginning on day 2 and day 5 after ferritin-H deletion, respectively, but was not excreted from the body. Plasma-(59)Fe was cleared significantly faster in iron-deficient Fth(Δ/Δ)-mice than in iron-adequate Fth(lox/lox)-controls. (59)Fe-distribution showed a transient peak (e.g., in heart, kidney, muscle) in Fth(lox/lox) control mice, but not in ferritin-H-deleted Fth(Δ/Δ) mice 24 hours after (59)Fe injection. (59)Fe uptake into the liver and spleen was significantly lower in iron-deficient Fth(Δ/Δ) than in Fth(lox/lox) mice 24 hours and 7 days after injection, respectively, and rapidly appeared in circulating erythrocytes instead. The rate of (59)Fe release after ferritin-H deletion supports earlier data on ferritin turnover in mammals; released (59)Fe is not excreted from the body. Instead, (59)Fe is channeled into erythropoiesis and circulating erythrocytes significantly more extensively and faster. Along with a lack of transient interim (59)Fe storage (e.g., in the heart and kidney), this finding is evidence for ferritin-related iron storage-capacity affecting rate and extent of iron utilization.