title: Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype.
abstract: Hepcidin is a 25-amino-acid peptide demonstrated to be the iron regulatory hormone capable of blocking iron absorption from the duodenum and iron release from macrophages. Mutations affecting hepcidin regulators or the hepcidin gene itself cause hemochromatosis, a common genetic disorder. Hepcidin is produced mainly by the liver, but many cells and tissues express low levels of the hormone. To determine the contribution of these hepcidin-producing tissues in body iron homeostasis, we have developed a new mouse model in which the hepcidin gene can be conditionally inactivated. Here we compare a liver-specific knockout (KO) mouse model with total KO mice. We show that the liver-specific KO mice fully recapitulate the severe iron overload phenotype observed in the total KO mice, with increased plasma iron and massive parenchymal iron accumulation. This result demonstrates that the hepatocyte constitutes the predominant reservoir for systemic hepcidin and that the other tissues are unable to compensate.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Zumerle
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Jacques R R
authors.initials: JR
authors.lastname: Mathieu
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Delga
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Heinis
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Viatte
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Peyssonnaux
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018390:Gene Targeting; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology; D064451:Hepcidins / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D010641:Phenotype
chemical_list: D064451:Hepcidins; D007501:Iron