A mouse model of juvenile hemochromatosis.

Published

Journal Article

Hereditary hemochromatosis is an iron-overload disorder resulting from mutations in proteins presumed to be involved in the maintenance of iron homeostasis. Mutations in hemojuvelin (HJV) cause severe, early-onset juvenile hemochromatosis. The normal function of HJV is unknown. Juvenile hemochromatosis patients have decreased urinary levels of hepcidin, a peptide hormone that binds to the cellular iron exporter ferroportin, causing its internalization and degradation. We have disrupted the murine Hjv gene and shown that Hjv-/- mice have markedly increased iron deposition in liver, pancreas, and heart but decreased iron levels in tissue macrophages. Hepcidin mRNA expression was decreased in Hjv-/- mice. Accordingly, ferroportin expression detected by immunohistochemistry was markedly increased in both intestinal epithelial cells and macrophages. We propose that excess, unregulated ferroportin activity in these cell types leads to the increased intestinal iron absorption and plasma iron levels characteristic of the juvenile hemochromatosis phenotype.

Full Text

Duke Authors

Cited Authors

  • Huang, FW; Pinkus, JL; Pinkus, GS; Fleming, MD; Andrews, NC

Published Date

  • August 2005

Published In

Volume / Issue

  • 115 / 8

Start / End Page

  • 2187 - 2191

PubMed ID

  • 16075059

Pubmed Central ID

  • 16075059

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI25049

Language

  • eng

Conference Location

  • United States