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A mouse model of juvenile hemochromatosis.

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.

Pubmed ID: 16075059

Authors

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

Journal

The Journal of clinical investigation

Publication Data

August 2, 2005

Associated Grants

  • Agency: NICHD NIH HHS, Id: P30 HD18655
  • Agency: NIDDK NIH HHS, Id: R01 DK 062474
  • Agency: NIDDK NIH HHS, Id: R01 DK 066373
  • Agency: NIDDK NIH HHS, Id: R01 DK066373
  • Agency: NIDDK NIH HHS, Id: R01 DK066373-02

Mesh Terms

  • Animals
  • Cation Transport Proteins
  • Disease Models, Animal
  • Hemochromatosis
  • Humans
  • Intestinal Mucosa
  • Intestines
  • Iron Overload
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Mutant Strains