title: Hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in mice.
abstract: 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 Tf(hpx/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 transferrin-independent hepcidin expression in conditions of iron overload.
authors: Department of Pathology, Children's Hospital, Boston, MA 02115, USA. tbartnikas@enders.tch.harvard.edu
authors: Thomas B
authors: TB
authors: Bartnikas
authors: Mark D
authors: MD
authors: Fleming
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014168:Transferrin / Q000172:deficiency* / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins; D014168:Transferrin