Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse

Vulpe, Christopher D., Kuo, Yien-Ming, Murphy, Therese L., Cowley, Lex, Askwith, Candice, Libina, Natasha, Gitschier, Jane and Anderson, Gregory J. (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nature Genetics, 21 2: 195-199. doi:10.1038/5979


Author Vulpe, Christopher D.
Kuo, Yien-Ming
Murphy, Therese L.
Cowley, Lex
Askwith, Candice
Libina, Natasha
Gitschier, Jane
Anderson, Gregory J.
Title Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse
Formatted title
Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
0028-0836
1746-4366
Publication date 1999-02
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/5979
Volume 21
Issue 2
Start page 195
End page 199
Total pages 5
Place of publication New York
Publisher Nature America .
Collection year 1999
Language eng
Subject C1
321006 Gastroenterology and Hepatology
730113 Digestive system and disorders
Formatted abstract
Iron is essential for many cellular functions; consequently, disturbances of iron homeostasis, leading to either iron deficiency or iron overload, can have significant clinical consequences. Despite the clinical prevalence of these disorders, the mechanism by which dietary iron is absorbed into the body is poorly understood. We have identified a key component in intestinal iron transport by study of the sex-linked anaemia (sla) mouse, which has a block in intestinal iron transport. Mice carrying the sla mutation develop moderate to severe microcytic hypochromic anaemia. Although these mice take up iron from the intestinal lumen into mature epithelial cells normally, the subsequent exit of iron into the circulation is diminished. As a result, iron accumulates in enterocytes and is lost during turnover of the intestinal epithelium. Biochemical studies have failed to identify the underlying difference between sla and normal mice, therefore, we used a genetic approach to identify the gene mutant in sla mice. We describe here a novel gene, Heph, encoding a transmembrane-bound ceruloplasmin homologue that is mutant in the sla mouse and highly expressed in intestine. We suggest that the hephaestin protein is a multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and that it is an important link between copper and iron metabolism in mammals.
Keyword Genetics & Heredity
Saccharomyces-cerevisiae
Fet3 Gene
Ferroxidase
Expression
Yeast
Q-Index Code C1

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collection: School of Medicine Publications
 
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Created: Tue, 10 Jun 2008, 13:26:05 EST