Hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in mice

Here we investigate the regulation of hepcidin, a hormone that inhibits dietary iron absorption and macrophage iron recycling, by the serum iron-binding protein transferrin. Mice deficient in transferrin (Tf-hpx/hpx) and hemojuvelin (Hjv(-/-)), a gene mutated in juvenile hemochromatosis, a disease of hepcidin deficiency and iron overload, were generated. While Tfhpx/hpx Hjv(+/+) and Tf-hpx/hpx Hjv(-/-) phenotypes did not differ markedly, transferrin treatment and RBC transfusions robustly increased hepcidin levels in Tf-hpx/hpx Hjv(+/+) but not Tf-hpx/hpx Hjv(-/-) mice. These results suggest that, while hemojuvelin is not essential for the establishment or maintenance of hepcidin deficiency in transferrin-deficient mice, hemojuvelin is essential for transferrin-dependent and tansferrin-independent hepcidin expression in conditions of iron overload.