Microcytic anemia, inherited as a unit autosomal recessive, is the first of the twelve known single-gene induced hereditary anemias of the mouse which results entirely from alteration of individual erythrocytes rather than from reduction in number of red cells. At all ages where mk/mk individuals could be recognized, from the fifteenth day of gestation to adulthood, the erythrocyte count of mk/mk individuals was at least as high as that of normal counterparts. At all ages, the hemoglobin concentration in these small erythrocytes was also reduced, so that the total available hemoglobin was markedly reduced at all ages. The higher than normal numbers of erythrocytes in adult microcytic mice demonstrate that the cell-producing mechanisms operate efficiently. Genetic tests have shown that the mk single-gene defect has no relation to structure of either the α-chain or the β-chain of the hemoglobin molecule. The mk microcytosis and hypochromia must then result from a metabolic or structural defect independent both of the factors responsible for regulating red cell number and of those controlling hemoglobin structure.
This mk/mk microcytic anemia shows some similarities to human thalassemias: hypochromia, microcytosis and presence of target cells, combined with splenomegaly, reticulocytosis, and higher than normal erythrocyte counts (like thalassemia minor). As in thalassemia, hemoglobin structure is normal, although the amount per cell is subnormal. Human hemolytic anemias also share some of these characteristics. The similarities of mk/mk microcytic anemia of the mouse to certain human anemias are sufficient to warrant its further investigation as an animal model for understanding of human hereditary disease.