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.

Haptoglobin modifies the hemochromatosis phenotype in mice / E., Tolosano; S., Fagoonee; Garuti, Cinzia; L., Valli; N. C., Andrews; F., Altruda; Pietrangelo, Antonello. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 105(8):(2005), pp. 3353-3355.

Haptoglobin modifies the hemochromatosis phenotype in mice

GARUTI, Cinzia;PIETRANGELO, Antonello
2005-01-01

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 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.
105(8)
3353
3355
Haptoglobin modifies the hemochromatosis phenotype in mice / E., Tolosano; S., Fagoonee; Garuti, Cinzia; L., Valli; N. C., Andrews; F., Altruda; Pietrangelo, Antonello. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 105(8):(2005), pp. 3353-3355.
E., Tolosano; S., Fagoonee; Garuti, Cinzia; L., Valli; N. C., Andrews; F., Altruda; Pietrangelo, Antonello
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/307478
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 32
social impact