Zebrafish as a model for defining the functional impact of mammalian ferroportin mutations.

Abstract

The term hemochromatosis represents a group of inherited disorders leading to iron overload. Mutations in HFE, HJV, and TfR2 cause autosomal-recessive forms of hemochromatosis. Mutations in ferroportin, however, result in dominantly inherited iron overload. Some mutations (H32R and N174I) in ferroportin lead to macrophage iron loading, while others (NI44H) lead to hepatocyte iron loading. Expression of H32R or N174I ferroportin cDNA in zebrafish leads to severe iron-limited erythropoiesis. Expression of wild-type ferroportin or hepcidin-resistant ferroportin (N144H) does not affect erythropoiesis. Zebrafish provides a facile way of identifying which ferroportin mutants may lead to macrophage iron loading.

• Authors: Ivana De Domenico, Michael B Vaughn, Donghoon Yoon, James P Kushner, Diane M Ward, Jerry Kaplan
• Journal: Blood (Blood) Vol. 110 Issue 10 Pg. 3780-3 (Nov 15 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17726163 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cation Transport Proteins
• metal transporting protein 1
• Iron

Topics

• Animals
• Cation Transport Proteins (genetics, physiology)
• Embryo, Nonmammalian
• Genetic Diseases, Inborn (etiology, genetics)
• Iron (metabolism)
• Macrophages (metabolism)
• Models, Animal
• Mutation (physiology)
• Zebrafish (genetics)