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

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