Hfe acts in hepatocytes to prevent hemochromatosis.
Hereditary hemochromatosis (HH) is a prevalent, potentially fatal disorder of iron metabolism hallmarked by intestinal hyperabsorption of iron, hyperferremia, and hepatic iron overload. In both humans and mice, type I HH is associated with mutations in the broadly expressed HFE/Hfe gene. To identify where Hfe acts to prevent HH, we generated mice with tissue-specific Hfe ablations. This work demonstrates that local Hfe expression in hepatocytes serves to maintain physiological iron homeostasis, answering a long-standing question in medicine and explaining earlier clinical observations.
Vujić Spasić
Maja
M
Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Kiss
Judit
J
Herrmann
Thomas
T
Galy
Bruno
B
Martinache
Stefanie
S
Stolte
Jens
J
Gröne
Hermann-Josef
HJ
Stremmel
Wolfgang
W
Hentze
Matthias W
MW
Muckenthaler
Martina U
MU
D000818:Animals; D006432:Hemochromatosis / Q000209:etiology*; D000071020:Hemochromatosis Protein; D022781:Hepatocytes / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation
D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron