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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4511-4517. Prepublished online as a Blood First Edition Paper on January 30, 2007; DOI 10.1182/blood-2006-07-036186. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-036186v1 109/10/4511    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 Spasic, M. V. Articles by Muckenthaler, M. U. Search for Related Content PubMed PubMed Citation Articles by Spasic, M. V. Articles by Muckenthaler, M. U. Related Collections Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Physiologic systemic iron metabolism in mice deficient for duodenal Hfe Maja Vujic Spasic1,2, Judit Kiss1,2, Thomas Herrmann3, Regina Kessler2, Jens Stolte4, Bruno Galy4, Birgit Rathkolb5, Eckhard Wolf5, Wolfgang Stremmel3, Matthias W. Hentze1,4, and Martina U. Muckenthaler1,2 1 Molecular Medicine Partnership Unit, University of Heidelberg, Germany; 2 Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Germany; 3 Department of Internal Medicine IV, University of Heidelberg, Germany; 4 European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; 5 German Mouse Clinic and Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilian-University, Munich, Germany Mutations in the Hfe gene result in hereditary hemochromatosis (HH), a disorder characterized by increased duodenal iron absorption and tissue iron overload. Identification of a direct interaction between Hfe and transferrin receptor 1 in duodenal cells led to the hypothesis that the lack of functional Hfe in the duodenum affects TfR1-mediated serosal uptake of iron and misprogramming of the iron absorptive cells. Contrasting this view, Hfe deficiency causes inappropriately low expression of the hepatic iron hormone hepcidin, which causes increased duodenal iron absorption. We specifically ablated Hfe expression in mouse enterocytes using Cre/LoxP technology. Mice with efficient deletion of Hfe in crypt- and villi-enterocytes maintain physiologic iron metabolism with wild-type unsaturated iron binding capacity, hepatic iron levels, and hepcidin mRNA expression. Furthermore, the expression of genes encoding the major intestinal iron transporters is unchanged in duodenal Hfe-deficient mice. Our data demonstrate that intestinal Hfe is dispensable for the physiologic control of systemic iron homeostasis under steady state conditions. These findings exclude a primary role for duodenal Hfe in the pathogenesis of HH and support the model according to which Hfe is required for appropriate expression of the "iron hormone" hepcidin which then controls intestinal iron absorption. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Crypt cell hypothesis: technical knock-out Robert E. Fleming Blood 2007 109: 4114-4115. [Full Text] [PDF] This article has been cited by other articles: L. Kautz, D. Meynard, C. Besson-Fournier, V. Darnaud, T. Al Saati, H. Coppin, and M.-P. Roth BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression Blood, September 17, 2009; 114(12): 2515 - 2520. [Abstract] [Full Text] [PDF] A.-S. Zhang and C. A. Enns Iron Homeostasis: Recently Identified Proteins Provide Insight into Novel Control Mechanisms J. Biol. Chem., January 9, 2009; 284(2): 711 - 715. [Abstract] [Full Text] [PDF] Pathogenesis of Hemochromatosis Journal Watch Oncology and Hematology, June 18, 2007; 2007(618): 4 - 4. [Full Text]

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