Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice

The hypotransferrinemic mouse (trf(hpx)) is a mutant strain exhibiting tran sferrin deficiency, marked anemia, hyperabsorption of iron, and elevated he patic iron stores, We set out to investigate the relative roles of anemia a nd of transferrin in the malregulation of intestinal iron absorption in the se animals, Transfusion of erythrocytes obtained from littermate controls i ncreased hemoglobin levels and reduced reticulocyte counts in recipient ani mals. Although mucosal to carcass Fe-59 transfer was reduced, total duodena l iron uptake was not significantly affected. Iron absorption in homozygote s, in contrast to littermate controls, was not reduced by hyperoxia, Mouse transferrin injections, in the short term, increased delivery of iron to th e marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls, Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduce d liver iron and intestinal iron absorption values in trfhpx animals. When such daily-injected mice were left for a week to allow transferrin clearanc e, iron absorption values were significantly enhanced; hemoglobin or hepati c iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trfhpx mice is not solely because of the a nemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa. (C) 1999 by The American Society of Hematology.