Distribution of injected iron 59 and manganese 54 in hypotransferrinemic mice

Transferrin has been proposed as the mobilization protein for iron and manganese. To better understand the role of transferrin in the transport of these metals, we studied the tissue distribution of injected iron 59 and manganese 54 in the hypotransferrinemic (Hp) mouse mutant. The Hp mouse has a mutation in the transferrin gene and produces < 1% of normal transferrin levels. The tissue distribution of 59Fe and 54Mn in Hp mice was compared with that in animals heterozygous for the Hp mutation (50% transferrin levels) and wild-type animals. Formed elements in the brain, liver, spleen, heart, sternum/rib, plasma, and blood were analyzed for isotope incorporation at 24 hours, 7 days, and 4 weeks after injection. Tissue distribution of both 59Fe and 54Mn was similar in wild-type and heterozygote animals, indicating that decreased transferrin concentration and increased saturation did not influence the tissue distribution of the injected metals. The absence of transferrin in the Hp mutant was associated with abnormal tissue distribution of radiolabeled iron; there was 4 times more 59Fe than normal in the Hp liver and 10 times less 59Fe in the spleen and blood formed elements than normal. Injected manganese also accumulated at abnormally high levels in the Hp mouse liver. Distribution of either metal to the brain, heart, and sternum/rib was not affected by the absence of plasma transferrin. These results reveal that transferrin is required for proper targeting of manganese and iron, especially from the liver to other organs, but further indicate that nontransferrin transport mechanisms for iron and manganese must exist.