Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice.
Hereditary hemochromatosis (HH) type I is a disorder of iron metabolism caused by a mutation in the HFE gene. Whereas the prevalence of the mutation is very high, its penetrance seems very low. The goal of our study was to determine whether hepcidin, a recently identified iron-regulatory peptide, could be a genetic modifier contributing to the HH phenotype. In mice, deficiency of either HFE (Hfe(-/-)) or hepcidin (Usf2(-/-)) is associated with the same pattern of iron overload observed in patients with HH. We intercrossed Hfe(-/-) and Usf2(+/-) mice and asked whether hepcidin deficiency increased the iron burden in Hfe(-/-) mice. Our results showed that, indeed, liver iron accumulation was greater in the Hfe(-/-)Usf2(+/-) mice than in mice lacking Hfe alone. This result, in agreement with recent findings in humans, provides a genetic explanation for some variability of the HH phenotype.
Nicolas
Gaël
G
INSERM 409, Faculté de Médecine Xavier Bichat, Paris, France.
Andrews
Nancy C
NC
Kahn
Axel
A
Vaulont
Sophie
S
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000172:deficiency* / Q000235:genetics*; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012313:RNA; D007501:Iron