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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3417-3425. Prepublished online as a Blood First Edition Paper on August 3, 2007; DOI 10.1182/blood-2006-11-057307. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-057307v1 110/9/3417    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Basu, P. Articles by Lloyd, J. A. Search for Related Content PubMed PubMed Citation Articles by Basu, P. Articles by Lloyd, J. A. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS EKLF and KLF2 have compensatory roles in embryonic ß-globin gene expression and primitive erythropoiesis Priyadarshi Basu1, Tina K. Lung1,2, Wafaa Lemsaddek1, Thanh Giang Sargent1, David C. Williams, Jr3,4, Mohua Basu1, Latasha C. Redmond1, Jerry B Lingrel5, Jack L. Haar2, and Joyce A. Lloyd1,4 1 Department of Human Genetics, 2 Department of Anatomy and Neurobiology, 3 Department of Pathology, and 4 Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; and 5 Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, OH The Krüppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Krüppel-like factor (EKLF or KLF1) regulates adult ß-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and ßh1-, but not adult ßglobin, gene expression in mice. Both EKLF and KLF2 play roles in primitive erythroid cell development. To investigate potential interactions between these genes, EKLF/KLF2 double-mutant embryos were analyzed. EKLF–/–KLF2–/– mice appear anemic at embryonic day 10.5 (E10.5) and die before E11.5, whereas single-knockout EKLF–/– or KLF2–/– embryos are grossly normal at E10.5 and die later than EKLF–/–KLF2–/– embryos. At E10.5, Ey- and ßh1-globin mRNA is greatly reduced in EKLF–/–KLF2–/–, compared with EKLF–/– or KLF2–/– embryos, consistent with the observed anemia. Light and electron microscopic analyses of E9.5 EKLF–/–KLF2–/– yolk sacs, and cytospins, indicate that erythroid and endothelial cells are morphologically more abnormal than in either single knockout. EKLF–/–KLF2–/– erythroid cells are markedly irregularly shaped, suggesting membrane abnormalities. EKLF and KLF2 may have coordinate roles in a common progenitor to erythroid and endothelial cells. The data indicate that EKLF and KLF2 have redundant functions in embryonic ß-like globin gene expression, primitive erythropoiesis, and endothelial development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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