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.

journal_name

Blood

journal_title

Blood

authors

Zumerle S,Mathieu JR,Delga S,Heinis M,Viatte L,Vaulont S,Peyssonnaux C

doi

10.1182/blood-2014-01-550467

subject

Has Abstract

pub_date

2014-06-05 00:00:00

pages

3646-50

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2014-01-550467

journal_volume

123

pub_type

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