title: Haptoglobin modifies the hemochromatosis phenotype in mice.
abstract: 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.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. emanuela. tolosano@unito.it
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.forename: Cinzia
authors.initials: C
authors.lastname: Garuti
authors.forename: Linda
authors.initials: L
authors.lastname: Valli
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andrews
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
mesh_terms: D000818:Animals; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism*; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019683:Penetrance; D010641:Phenotype
chemical_list: D006242:Haptoglobins; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron