Haptoglobin modifies the hemochromatosis phenotype in mice

被引:28
作者
Tolosano, E
Fagoonee, S
Garuti, C
Valli, L
Andrews, NC
Altruda, F
Pietrangelo, A
机构
[1] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy
[2] San Giovanni Battista Hosp, Expt Med Res Ctr, Turin, Italy
[3] Univ Modena & Reggio Emilia, Ctr Hemochromatosis, Dept Internal Med, Modena, Italy
[4] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA
[5] Howard Hughes Med Inst, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Boston, MA USA
关键词
D O I
10.1182/blood-2004-07-2814
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 glomerull 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.
引用
收藏
页码:3353 / 3355
页数:3
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