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Blood, 15 May 2005, Vol. 105, No. 10, pp. 4096-4102. Prepublished online as a Blood First Edition Paper on February 3, 2005; DOI 10.1182/blood-2004-11-4502. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4502v1 105/10/4096    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schimanski, L. M. Articles by Townsend, A. R. M. Search for Related Content PubMed PubMed Citation Articles by Schimanski, L. M. Articles by Townsend, A. R. M. Related Collections Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations Lisa M. Schimanski, Hal Drakesmith, Alison T. Merryweather-Clarke, Vip Viprakasit, Jon P. Edwards, Emma Sweetland, Judy M. Bastin, Diana Cowley, Yingyong Chinthammitr, Kathryn J. H. Robson, and Alain R. M. Townsend From the Molecular Immunology Group, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; the MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; the Department of Paediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; and the Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Type IV hemochromatosis is associated with dominant mutations in the SLC40A1 gene encoding ferroportin (FPN). Known as the "ferroportin disease," this condition is typically characterized by high serum ferritin, reduced transferrin saturation, and macrophage iron loading. Previously FPN expression in vitro has been shown to cause iron deficiency in human cell lines and mediate iron export from Xenopus oocytes. We confirm these findings by showing that expression of human FPN in a human cell line results in an iron deficiency because of a 3-fold increased export of iron. We show that FPN mutations A77D, V162, and G490D that are associated with a typical pattern of disease in vivo cause a loss of iron export function in vitro but do not physically or functionally impede wild-type FPN. These mutants may, therefore, lead to disease by haploinsufficiency. By contrast the variants Y64N, N144D, N144H, Q248H, and C326Y, which can be associated with greater transferrin saturation and more prominent iron deposition in liver parenchyma in vivo, retained iron export function in vitro. Because FPN is a target for negative feedback in iron homeostasis, we postulate that the latter group of mutants may resist inhibition, resulting in a permanently "turned on" iron exporter. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ferroportin mutations: a tale of two phenotypes Elizabeta Nemeth Blood 2005 105: 3763-3764. [Full Text] [PDF] This article has been cited by other articles: A. Fernandes, G. C. Preza, Y. Phung, I. De Domenico, J. Kaplan, T. Ganz, and E. Nemeth The molecular basis of hepcidin-resistant hereditary hemochromatosis Blood, July 9, 2009; 114(2): 437 - 443. [Abstract] [Full Text] [PDF] C. Y. Lok, A. T. Merryweather-Clarke, V. Viprakasit, Y. Chinthammitr, S. 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