Hemopoietic progenitor cells in marrow and spleen of mice with hereditary iron deficiency anemia.

T HE MUTATION responsible for sex-linked anemia of mice (gene symbol, sla) was produced by X-radiation in a noninbred stock of house mouse.’ The anemia is hypochromic and microcytic. In young anemic mice ( hemizygous males, sla/ -and homozygous females, sla/ sla ) the blood hemoglobin concentration varies from 5 to 8 Gm. per 100 ml.24 Histochemical studies of the iron stores revealed depletion in anemic mice,5 confirmed by chemical estimations of the total body iron content.#{176} Parenteral treatment with iron dextran cures the anemia.3’4 Further investigations of iron metabolism support the suggestion that X-linked anemia is a consequence of tissue iron deficiency. Histochemical studies of the small intestinal mucosa in anemic mice showed excessive accumulation ( retention? ) of iron in the epithelial cells in spite of depletion of body iron stores;5 also, retention of oral tracer doses of radio-iron was decreased.#{176} Thus, the sla gene appears to cause iron deficiency anemia as a result of malabsorption of iron.5’6 In the experiments to be described here, marrow and spleen cells of sla/anemic male mice have been transplanted into irradiated histocompatible recipients to study 1 ) the proliferative and differentiating capacity of sla/progenitor cells, 2 ) the quality of mature erythrocytes produced by sla/progenitor cells in irradiated hosts which were not iron deficient, and 3) the nature of new progenitor cells produced by sla/marrow cells in such host mice. The results exclude a primary defect in erythropoiesis by sla/progenitor cells but show the influence of tissue iron deficiency on stem cell behavior. The results also indicate that separate unipotent progenitor cells for erythropoiesis and leukopoiesis exist in the marrow and spleen of mice; such progenitor cells in the marrow are capable of self-replication.