Diminished acquisition of iron by reticulocytes from mice with hemoglobin deficit.

Reticulocyte iron and transferrin uptake was studied in hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse characterized by hypochromic microcytic anemia, reticulocytosis, hyperferremia, and increased red-cell-free protoporphyrin. Reticulocyte-rich red cells were incubated in vitro in a mixture of 125I-labeled diferric mouse transferrin and 59Fe-labeled iron-saturated mouse plasma. At 37 degrees C, the uptake of transferrin by reticulocytes from affected animals (15 ng/micrograms RNA) was the same as that of reticulocytes from control animals. However, the uptake of iron by affected reticulocytes (0.11 ng/micrograms RNA) was significantly lower than that by control reticulocytes (0.24). At 4 degrees C, transferrin binding by affected and control reticulocytes was again indistinguishable. The deficiency in the uptake of iron by affected reticulocytes was not observed on incubation at 4 degrees C. Scatchard analysis of transferrin receptors on hbd/hbd and control reticulocytes showed no difference in pKD and a slight elevation in number of receptors per reticulocyte for hbd/hbd animals. These findings suggest that hbd/hbd reticulocytes have a defect in iron acquisition that is distal to the binding of transferrin to the cell membrane receptor. This defect is similar to one already described in the anemia of the Belgrade laboratory rat.