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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-11-0037. This Article Full Text (PDF) All Versions of this Article: 2001-11-0037v1 100/4/1465    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 Ajioka, R. S Articles by Kushner, J. P Search for Related Content PubMed PubMed Citation Articles by Ajioka, R. S Articles by Kushner, J. P Social Bookmarking                   What's this? Submitted November 27, 2001 Accepted April 3, 2002 Regulation of Iron Absorption in Hfe Mutant Mice Richard S Ajioka*, Joanne E Levy, Nancy C Andrews, and James P Kushner Div. of Hematology Dept. of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA Div. of Hematology/Oncology Dept. of Pediatrics, Children's Hospital Harvard University, Boston, MA, USA; Div. of Hematology Dept. of Pediatrics, Brigham and Women's Hospital, Boston, MA, USA Div. of Hematology/Oncology Dept. of Pediatrics, Children's Hospital Harvard University, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA * Corresponding author; email: richard.ajioka{at}hsc.utah.edu. Hereditary hemochromatosis is most commonly caused by homozygosity for a point mutation (C282Y) in the HFE gene. The mechanism by which HFE regulates iron absorption is not known but the C282Y mutation results in loss of cell surface expression of HFE protein and hyperabsorption of iron by the duodenal enterocyte. Mice homozygous for a deletion in the Hfe gene or a mutation equivalent to that seen in human hereditary hemochromatosis (C282Y) were compared with wild type animals for their ability to regulate iron absorption. Both mutant strains hyperabsorbed 59Fe administered by gavage. Feeding a diet supplemented with carbonyl iron resulted in a greater than five-fold reduction of 59Fe absorption in both wild type and mutant mouse strains. Similarly, the iron loading associated with age in Hfe mutant mice resulted in nearly a four-fold reduction in iron absorption. When mice were stimulated to absorb iron either by depleting iron stores or by inducing erythropoiesis, wild type and Hfe mutant strains increased absorption to similar levels, approximately five-fold over control values. Our data indicate that Hfe mutant mice retain the ability to regulate iron absorption. Hfe protein plays a minor role in down regulation but does not influence the up regulation of iron absorption. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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] M. Constante, D. Wang, V.-A. Raymond, M. Bilodeau, and M. M. Santos Repression of Repulsive Guidance Molecule C during Inflammation Is Independent of Hfe and Involves Tumor Necrosis Factor-{alpha} Am. J. Pathol., February 1, 2007; 170(2): 497 - 504. [Abstract] [Full Text] [PDF] S. F. Drake, E. H. Morgan, C. E. Herbison, R. Delima, R. M. Graham, A. C. G. Chua, P. J. Leedman, R. E. Fleming, B. R. Bacon, J. 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