title: Hfe acts in hepatocytes to prevent hemochromatosis.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Vujić Spasić
authors.forename: Judit
authors.initials: J
authors.lastname: Kiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Bruno
authors.initials: B
authors.lastname: Galy
authors.forename: Stefanie
authors.initials: S
authors.lastname: Martinache
authors.forename: Jens
authors.initials: J
authors.lastname: Stolte
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
mesh_terms: 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
chemical_list: D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron