Hemopoietic Progenitor Cells in Marrow and Spleen of Mice with Hereditary Iron Deficiency Anemia

Abstract

Abstract Sex-linked hypochromic anemia is the result of iron deficiency, apparently caused by malabsorption of iron. Progenitor cells in marrow and spleen of male anemic (genotype, sla/-) and normal (+/-) littermate mice were studied by quantitative transplantation into irradiated, but otherwise normal, recipient mice. The progeny of grafted cells were assessed by isotope uptake technics. Progenitor cells of sla/- mice were capable of extensive production of erythroid cells, which synthesized DNA and hemoglobin, and of leukocytic elements, which synthesized DNA but not hemoglobin. Proliferation of the latter cell types was assayed in recipient mice rendered polycythemic with red cell infusions to suppress erythropoiesis. The mature red cells produced by transplanted sla/- marrow and spleen were normal with respect to volume, size, and hemoglobin content. The grossly enlarged spleens of sla/- mice contained 20 times the normal number of erythropoietic progenitor units (EPU); parenteral iron therapy cured the anemia and caused the spleen to revert to normal. The ratio of EPU to leukopoietic progenitor units (LPU) was abnormally high in marrow and spleen of sla/- mice; in addition, the EPU:LPU ratio was higher in spleen than in marrow of normal and anemic mice. The high EPU:LPU ratio of sla/- bone marrow persisted after transplantation to a lesser, but significant, extent for at least 52 days. We conclude that: 1) the sla mutant gene does not affect hemopoietic cells directly, but that iron deficiency alters the ratio of EPU to LPU by committing more primitive pluripotent stem cells to erythropoiesis, and 2) EPU and LPU are separate progenitor cells with restricted potential for differentiation. Persistence of the altered EPU:LPU ratio in sla/- marrow chimeras may be explained by extensive and independent self-replication of EPU and/or LPU, especially after grafting relatively small numbers (1.6 million) of marrow cells into irradiated mice.