Marrow Transplantation and Iron Therapy in Mouse Hereditary Microcytic Anemia

The defective tissues causing the microcytic anemia in mk/mk mice have been studied by transplantation of marrow erythrocyte precursors into lethally irradiated recipients. Microcytic (mk/mk) marrow in irradiated normal mice produced erythrocyte parameters, blood values, spleen/body weight ratios, and reticulocyte percentages characteristic of the microcytic anemia, but splenic iron stores remained high. Normal marrow in irradiated microcytic mice produced erythrocyte parameters intermediate between microcytic and normal and, combined with iron injections, produced normal erythrocyte parameters, blood values, spleen/body weight ratios, and reticulocyte percentages; long-term splenic iron stores remained low. Iron injections did not improve blood values of either irradiated normal mice implanted with microcytic marrow or untreated microcytic mice. Microcytic mice injected with iron recovered more rapidly from repeated severe bleedings than did uninjected microcytic mice, but iron injections made no difference in final blood values reached. Only slightly less ⁵⁹Fe remained in mk/mk than in normal mice 22 days after injection. These results indicate that not only the erythrocyte precursor cells but also iron supplies to these cells and splenic iron stores are defective in microcytic mice and that iron loss is not responsible for the iron storage defect.