Haptoglobin modifies the hemochromatosis phenotype in mice.


Journal Article

Classic hereditary hemochromatosis (HH) is a common genetic disorder of iron metabolism caused by a mutation in the HFE gene. Whereas the prevalence of the mutation is very high, the clinical penetrance of the disease is low, suggesting that the HFE mutation is a necessary but not sufficient cause of clinical HH. Several candidate modifier genes have been proposed in mice and humans, including haptoglobin. Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. It delivers free plasma hemoglobin to the reticuloendothelial system, thus reducing loss of hemoglobin through the glomeruli and allowing heme-iron recycling. To gain insight into the role of haptoglobin as a modifier gene in HH, we used Hfe and haptoglobin double-null mice. Here, we show that Hfe and haptoglobin compound mutant mice accumulate significantly less hepatic iron than Hfe-null mice, thus demonstrating that haptoglobin-mediated heme-iron recovery may contribute significantly to iron loading in HH.

Full Text

Duke Authors

Cited Authors

  • Tolosano, E; Fagoonee, S; Garuti, C; Valli, L; Andrews, NC; Altruda, F; Pietrangelo, A

Published Date

  • April 15, 2005

Published In

Volume / Issue

  • 105 / 8

Start / End Page

  • 3353 - 3355

PubMed ID

  • 15613548

Pubmed Central ID

  • 15613548

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2004-07-2814


  • eng

Conference Location

  • United States