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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2952-2958. Prepublished online as a Blood First Edition Paper on December 8, 2005; DOI 10.1182/blood-2005-10-4071. This Article Full Text (PDF) All Versions of this Article: 2005-10-4071v1 107/7/2952    most recent Alert me when this article is cited Alert me if a correction is posted 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 Viatte, L. Articles by Vaulont, S. Search for Related Content PubMed PubMed Citation Articles by Viatte, L. Articles by Vaulont, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 12, 2005 Accepted November 23, 2005 Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice Lydie Viatte, Gael Nicolas, Dan-Qing Lou, Myriam Bennoun, Jeanne-Claire Lesbordes-Brion, Francois Canonne-Hergaux, Kai Schonig, Hermann Bujard, Axel Kahn, Nancy C Andrews, and Sophie Vaulont* Departement de Genetique, Developpement et Pathologie Moleculaire, Institut Cochin, F-75014 France. Inserm, U567, Paris, F-75014 France.CNRS, UMR 8104, Paris, F-75014 France. Universite Paris Descartes, Faculte de Medecine Rene Descartes, UMR-S 8104, Paris, F-75014 France., Paris, France Institut National de la Transfusion Sanguine, Paris, France Inserm, U409, Faculte de Medecine Xavier Bichat, Paris, France Zentrum fur Molekulare Biologie, Heidelberg, Germany Childrens Hospital Boston, Dana-Farber Cancer Institute, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts, USA * Corresponding author; email: vaulont{at}cochin.inserm.fr. We report the generation of a tetracycline-regulated (Tet ON) transgenic mouse model for acute and chronic expression of the iron regulatory peptide hepcidin in the liver. We demonstrate that short-term and long-term tetracycline-dependent activation of hepcidin in adult mice leads to hypoferremia and iron-limited erythropoiesis, respectively. This clearly establishes the key role of hepcidin in regulating the extracellular iron concentration. We previously demonstrated that, when expressed early in fetal development, constitutive transgenic hepcidin expression prevented iron accumulation in an Hfe-/- mouse model of hemochromatosis. We now explore the effect of chronic hepcidin expression in adult Hfe-/- mice that have already developed liver iron overload. We demonstrate that induction of chronic hepcidin expression in two month old Hfe-/- mice alters their pattern of cellular iron accumulation, leading to increased iron in tissue macrophages and duodenal cells but less iron in hepatocytes. This hepcidin-induced changes in the pattern of cellular iron accumulation are associated with decreased expression of the iron exporter ferroportin in macrophages but no detectable alteration of ferroportin expression in the hepatocytes. We speculate that this change in iron homeostasis could offer a therapeutic advantage by protecting against damage to parenchymal cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Treating iron overload with hepcidin Clara Camaschella Blood 2006 107: 2595. [Full Text] [PDF] This article has been cited by other articles: B. Chung, T. Chaston, J. Marks, S. K. Srai, and P. A. Sharp Hepcidin Decreases Iron Transporter Expression in Vivo in Mouse Duodenum and Spleen and in Vitro in THP-1 Macrophages and Intestinal Caco-2 Cells J. Nutr., August 1, 2009; 139(8): 1457 - 1462. [Abstract] [Full Text] [PDF] A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF] T Chaston, B Chung, M Mascarenhas, J Marks, B Patel, S K Srai, and P Sharp Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells Gut, March 1, 2008; 57(3): 374 - 382. [Abstract] [Full Text] [PDF] M. D. Fleming The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism Hematology, January 1, 2008; 2008(1): 151 - 158. [Abstract] [Full Text] [PDF] C. N. Roy, H. H. Mak, I. Akpan, G. Losyev, D. Zurakowski, and N. C. Andrews Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation Blood, May 1, 2007; 109(9): 4038 - 4044. [Abstract] [Full Text] [PDF] T. Ganz Molecular Control of Iron Transport J. Am. Soc. Nephrol., February 1, 2007; 18(2): 394 - 400. [Abstract] [Full Text] [PDF] D. W. Swinkels, M. C.H. Janssen, J. Bergmans, and J. J.M. Marx Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches Clin. Chem., June 1, 2006; 52(6): 950 - 968. [Abstract] [Full Text] [PDF] T. Ganz Hepcidin and Its Role in Regulating Systemic Iron Metabolism Hematology, January 1, 2006; 2006(1): 29 - 35. [Abstract] [Full Text] [PDF] P. Brissot and F. de Bels Current Approaches to the Management of Hemochromatosis Hematology, January 1, 2006; 2006(1): 36 - 41. [Abstract] [Full Text] [PDF]

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