SEARCH:   Advanced

This Article Full Text Full Text (PDF) 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 Perkins, A. C. Articles by Orkin, S. H. Search for Related Content PubMed PubMed Citation Articles by Perkins, A. C. Articles by Orkin, S. H. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 95 No. 5 (March 1), 2000: pp. 1827-1833 Fetal expression of a human A globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos A. C. Perkins, K. R. Peterson, G. Stamatoyannopoulos, H. E. Witkowska, and S. H. Orkin From the Children's Hospital and the Howard Hughes Medical Research Institute, and Harvard Medical School, Boston, MA; the Department of Biochemistry and Molecular Biology, School of Medicine, University of Kansas Medical Center, Kansas City, KS; the Children's Hospital Oakland Research Institute, Oakland, CA; the Division of Medical Genetics, University of Washington, Seattle, WA; and the Department of Physiology, Monash University, Melbourne, Australia. Mice lacking the erythroid Kruppel-like factor (EKLF) die in utero at embryonic day 15 (E15) from severe anemia. EKLF/ embryos display a marked deficit in -globin gene expression. To test whether -globin deficiency was solely responsible for the anemia and intrauterine death, we corrected the globin chain imbalance in EKLF/ embryos by breeding with a strain of mice that express high levels of human -globin. Despite efficient production of hybrid m2-h2 hemoglobin in the fetal livers of EKLF/ animals, hemolysis was not corrected and survival was not prolonged. We concluded that deficiency of nonglobin EKLF target genes is a major contributor to the definitive red blood cell abnormalities and prenatal death in EKLF/ embryos. These results suggest that strategies designed to antagonize EKLF function in adults with hemoglobinopathy, in an attempt to reactivate -globin gene expression, may adversely affect other essential aspects of red blood cell physiology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. P. W. Funnell, C. A. Maloney, L. J. Thompson, J. Keys, M. Tallack, A. C. Perkins, and M. Crossley Erythroid Kruppel-Like Factor Directly Activates the Basic Kruppel-Like Factor Gene in Erythroid Cells Mol. Cell. Biol., April 1, 2007; 27(7): 2777 - 2790. [Abstract] [Full Text] [PDF] A. M. Pilon, D. G. Nilson, D. Zhou, J. Sangerman, T. M. Townes, D. M. Bodine, and P. G. Gallagher Alterations in expression and chromatin configuration of the alpha hemoglobin-stabilizing protein gene in erythroid kruppel-like factor-deficient mice. Mol. Cell. Biol., June 1, 2006; 26(11): 4368 - 4377. [Abstract] [Full Text] [PDF] D. Hodge, E. Coghill, J. Keys, T. Maguire, B. Hartmann, A. McDowall, M. Weiss, S. Grimmond, and A. Perkins A global role for EKLF in definitive and primitive erythropoiesis Blood, April 15, 2006; 107(8): 3359 - 3370. [Abstract] [Full Text] [PDF] R. Drissen, M. von Lindern, A. Kolbus, S. Driegen, P. Steinlein, H. Beug, F. Grosveld, and S. Philipsen The Erythroid Phenotype of EKLF-Null Mice: Defects in Hemoglobin Metabolism and Membrane Stability Mol. Cell. Biol., June 15, 2005; 25(12): 5205 - 5214. [Abstract] [Full Text] [PDF] X. Chen and J. J. Bieker Stage-Specific Repression by the EKLF Transcriptional Activator Mol. Cell. Biol., December 1, 2004; 24(23): 10416 - 10424. [Abstract] [Full Text] [PDF] B. F. Hinnebusch, A. Siddique, J. W. Henderson, M. S. Malo, W. Zhang, C. P. Athaide, M. A. Abedrapo, X. Chen, V. W. Yang, and R. A. Hodin Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G23 - G30. [Abstract] [Full Text] [PDF] K. Pandya and T. M. Townes Basic Residues within the Kruppel Zinc Finger DNA Binding Domains Are the Critical Nuclear Localization Determinants of EKLF/KLF-1 J. Biol. Chem., May 3, 2002; 277(18): 16304 - 16312. [Abstract] [Full Text] [PDF] X. Chen and J. J. Bieker Unanticipated Repression Function Linked to Erythroid Kruppel-Like Factor Mol. Cell. Biol., May 1, 2001; 21(9): 3118 - 3125. [Abstract] [Full Text] E. Coghill, S. Eccleston, V. Fox, L. Cerruti, C. Brown, J. Cunningham, S. Jane, and A. Perkins Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice Blood, March 15, 2001; 97(6): 1861 - 1868. [Abstract] [Full Text] [PDF] K. Pandya, D. Donze, and T. M. Townes Novel Transactivation Domain in Erythroid Kruppel-like Factor (EKLF) J. Biol. Chem., March 9, 2001; 276(11): 8239 - 8243. [Abstract] [Full Text] [PDF]

	Copyright © 2000 by American Society of Hematology         Online ISSN: 1528-0020