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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4174-4180. Prepublished online as a Blood First Edition Paper on February 8, 2007; DOI 10.1182/blood-2007-01-066068. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-066068v1 109/10/4174    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 Zohn, I. E. Articles by Kaplan, J. Search for Related Content PubMed PubMed Citation Articles by Zohn, I. E. Articles by Kaplan, J. Related Collections Hematopoiesis and Stem Cells Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease Irene E. Zohn1, Ivana De Domenico2, Andrew Pollock1, Diane McVey Ward2, Jessica F. Goodman1, Xiayun Liang3, Amaru J. Sanchez1, Lee Niswander1, and Jerry Kaplan2 1 Howard Hughes Medical Institute, Department of Pediatrics, Section of Developmental Biology, University of Colorado at Denver and Health Sciences Center, Aurora; 2 Department of Pathology, School of Medicine, University of Utah, Salt Lake City; 3 Department of Pathology, University of Colorado Health Sciences Center, Denver Ferroportin disease is caused by mutation of one allele of the iron exporter ferroportin (Fpn/IREG1/Slc40a1/MTP1). All reported human mutations are missense mutations and heterozygous null mutations in mouse Fpn do not recapitulate the human disease. Here we describe the flatiron (ffe) mouse with a missense mutation (H32R) in Fpn that affects its localization and iron export activity. Similar to human patients with classic ferroportin disease, heterozygous ffe/+ mice present with iron loading of Kupffer cells, high serum ferritin, and low transferrin saturation. In macrophages isolated from ffe/+ heterozygous mice and through the use of Fpn plasmids with the ffe mutation, we show that Fpnffe acts as a dominant negative, preventing wild-type Fpn from localizing on the cell surface and transporting iron. These results demonstrate that mutations in Fpn resulting in protein mislocalization act in a dominant-negative fashion to cause disease, and the Fpnffe mouse represents the first mouse model of ferroportin disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Of mice and iron: ferroportin disease Nancy C. Andrews Blood 2007 109: 4115. [Full Text] [PDF] This article has been cited by other articles: I. De Domenico, E. Lo, D. M. Ward, and J. Kaplan Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2 PNAS, March 10, 2009; 106(10): 3800 - 3805. [Abstract] [Full Text] [PDF] N. C. Andrews Forging a field: the golden age of iron biology Blood, July 15, 2008; 112(2): 219 - 230. [Full Text] [PDF] I. De Domenico, M. B. Vaughn, D. Yoon, J. P. Kushner, D. M. Ward, and J. Kaplan Zebrafish as a model for defining the functional impact of mammalian ferroportin mutations Blood, November 15, 2007; 110(10): 3780 - 3783. [Abstract] [Full Text] [PDF]

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