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Blood, 1 September 2008, Vol. 112, No. 5, pp. 2071-2080. Prepublished online as a Blood First Edition Paper on June 13, 2008; DOI 10.1182/blood-2007-12-127480. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2007-12-127480v1 112/5/2071    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 Zhu, B.-M. Articles by Hennighausen, L. Search for Related Content PubMed PubMed Citation Articles by Zhu, B.-M. Articles by Hennighausen, L. Related Collections Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Hematopoietic-specific Stat5-null mice display microcytic hypochromic anemia associated with reduced transferrin receptor gene expression Bing-Mei Zhu*,1, Sara K. McLaughlin*,2, Risu Na1, Jie Liu3, Yongzhi Cui1, Cyril Martin1, Akiko Kimura1, Gertraud W. Robinson1, Nancy C. Andrews2, and Lothar Hennighausen1 1 Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD), National Institutes of Health (NIH), Bethesda, MD; 2 Children's Hospital Boston and Harvard Medical School, Boston, MA; and 3 ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD Iron is essential for all cells but is toxic in excess, so iron absorption and distribution are tightly regulated. Serum iron is bound to transferrin and enters erythroid cells primarily via receptor-mediated endocytosis of the transferrin receptor (Tfr1). Tfr1 is essential for developing erythrocytes and reduced Tfr1 expression is associated with anemia. The transcription factors STAT5A/B are activated by many cytokines, including erythropoietin. Stat5a/b–/– mice are severely anemic and die perinatally, but no link has been made to iron homeostasis. To study the function of STAT5A/B in vivo, we deleted the floxed Stat5a/b locus in hematopoietic cells with a Tie2-Cre transgene. These mice exhibited microcytic, hypochromic anemia, as did lethally irradiated mice that received a transplant of Stat5a/b–/– fetal liver cells. Flow cytometry and RNA analyses of erythroid cells from mutant mice revealed a 50% reduction in Tfr1 mRNA and protein. We detected STAT5A/B binding sites in the first intron of the Tfr1 gene and found that expression of constitutively active STAT5A in an erythroid cell line increased Tfr1 levels. Chromatin immunoprecipitation experiments confirmed the binding of STAT5A/B to these sites. We conclude that STAT5A/B is an important regulator of iron update in erythroid progenitor cells via its control of Tfr1 transcription. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: GASing up iron delivery via STAT5 Jeffrey S. Friedman Blood 2008 112: 1553-1554. [Full Text] [PDF] This article has been cited by other articles: A. Kimura, M. A. Rieger, J. M. Simone, W. Chen, M. C. Wickre, B.-M. Zhu, P. S. Hoppe, J. J. O'Shea, T. Schroeder, and L. Hennighausen The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis Blood, November 19, 2009; 114(21): 4721 - 4728. [Abstract] [Full Text] [PDF] P. Robach, S. Recalcati, D. Girelli, C. Gelfi, N. J. Aachmann-Andersen, J. J. Thomsen, A. M. Norgaard, A. Alberghini, N. Campostrini, A. Castagna, et al. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin Blood, June 25, 2009; 113(26): 6707 - 6715. [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] A. T. J. Wierenga, E. Vellenga, and J. J. Schuringa Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels Mol. Cell. Biol., November 1, 2008; 28(21): 6668 - 6680. [Abstract] [Full Text] [PDF] M. A. Kerenyi, F. Grebien, H. Gehart, M. Schifrer, M. Artaker, B. Kovacic, H. Beug, R. Moriggl, and E. W. Mullner Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1 Blood, November 1, 2008; 112(9): 3878 - 3888. [Abstract] [Full Text] [PDF]

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