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

The objective was to explore how ferritin-H deletion influences59 Fe-distribution and excretion-kinetics in mice. Kinetics of59 Fe-release from organs, whole-body excretion, and distribution-kinetics of intravenously injected59 Fe trace amounts were compared in iron-deficient and iron-replete mice with (FthΔ/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 FthΔ/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 FthΔ/Δ mice 24 hours after59 Fe injection.59 Fe uptake into the liver and spleen was significantly lower in iron-deficient FthΔ/Δ than in Fth lox/lox mice 24 hours and 7 days after injection, respectively, and rapidly appeared in circulating erythrocytes instead. The rate of59 Fe release after ferritin-H deletion supports earlier data on ferritin turnover in mammals; released59 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 interim59 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.