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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2401-2410. Prepublished online as a Blood First Edition Paper on July 24, 2009; DOI 10.1182/blood-2009-04-214619. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-04-214619v1 114/12/2401    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 Google Scholar Articles by Stumpo, D. J. Articles by Blackshear, P. J. PubMed PubMed Citation Articles by Stumpo, D. J. Articles by Blackshear, P. J. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis Deborah J. Stumpo1, Hal E. Broxmeyer2,3, Toni Ward1, Scott Cooper2,3, Giao Hangoc2,3, Yang Jo Chung4, William C. Shelley5,6, Eric K. Richfield7,8, Manas K. Ray9, Mervin C. Yoder5,6, Peter D. Aplan4, and Perry J. Blackshear1,10 1 Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC; 2 Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis; 3 Walther Oncology Center, Indiana University School of Medicine, Indianapolis; 4 Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD; 5 Department of Pediatrics, Indiana University School of Medicine, Indianapolis; 6 Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis; 7 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ; 8 Molecular Histology Center, Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry, Piscataway, NJ; 9 Knock Out Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC; and 10 Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC Members of the tristetraprolin family of tandem CCCH finger proteins can bind to AU-rich elements in the 3'-untranslated region of mRNAs, leading to their deadenylation and subsequent degradation. Partial deficiency of 1 of the 4 mouse tristetraprolin family members, Zfp36l2, resulted in complete female infertility because of early embryo death. We have now generated mice completely deficient in the ZFP36L2 protein. Homozygous Zfp36l2 knockout (KO) mice died within approximately 2 weeks of birth, apparently from intestinal or other hemorrhage. Analysis of peripheral blood from KO mice showed a decrease in red and white cells, hemoglobin, hematocrit, and platelets. Yolk sacs from embryonic day 11.5 (E11.5) Zfp36l2 KO mice and fetal livers from E14.5 KO mice gave rise to markedly reduced numbers of definitive multilineage and lineage-committed hematopoietic progenitors. Competitive reconstitution experiments demonstrated that Zfp36l2 KO fetal liver hematopoietic stem cells were unable to adequately reconstitute the hematopoietic system of lethally irradiated recipients. These data establish Zfp36l2 as a critical modulator of definitive hematopoiesis and suggest a novel regulatory pathway involving control of mRNA stability in the life cycle of hematopoietic stem and progenitor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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