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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5109-5117. Prepublished online as a Blood First Edition Paper on March 11, 2008; DOI 10.1182/blood-2007-05-091579. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-091579v1 111/10/5109    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 Xing, S. Articles by Zhao, Z. J. Search for Related Content PubMed PubMed Citation Articles by Xing, S. Articles by Zhao, Z. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 21, 2007 Accepted March 8, 2008 Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice Shu Xing, Wanting Tina Ho, Wanming Zhao, Junfeng Ma, Shaofeng Wang, Xuesong Xu, Qingshan Li, Xueqi Fu, Mingjiang Xu, and Zhizhuang Joe Zhao* Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun, China Clinical Laboratory, China Japan Union Hospital, Jilin University, Changchun, China Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY, United States * Corresponding author; email: joe-zhao{at}ouhsc.edu. The JAK2V617F mutation was found in most patients with myeloproliferative disorders (MPDs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We have generated transgenic mice expressing the mutated enzyme in the hematopoietic system driven by a vav gene promoter. The mice are viable and fertile. One line of the transgenic mice, which expressed a lower level of JAK2V617F, showed moderate elevations of blood cell counts, while another line with a higher level of JAK2V617F expression displayed marked increases in blood counts and developed phenotypes that closely resembled human ET and PV. The latter line of mice also developed PMF-like symptoms as they aged. The transgenic mice showed erythroid, megakaryocytic, and granulocytic hyperplasia in the bone marrow and spleen, displayed splenomegaly, and had reduced levels of plasma erythropoietin and thrombopoietin. They possessed an increased number of hematopoietic progenitor cells in peripheral blood, spleen, and bone marrow, and these cells formed autonomous colonies in the absence of growth factors and cytokines. The data show that JAK2V617F can cause MPDs in mice. Our study thus provides a mouse model to study the pathological role of JAK2V617F and to develop treatment for MPDs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Li, K. L. Miskimen, Z. Wang, X. Y. Xie, J. Brenzovich, J. J. Ryan, W. Tse, R. Moriggl, and K. D. Bunting STAT5 requires the N-domain for suppression of miR15/16, induction of bcl-2, and survival signaling in myeloproliferative disease Blood, February 18, 2010; 115(7): 1416 - 1424. [Abstract] [Full Text] [PDF] J. D. Merker, C. D. Jones, S. T. Oh, I. Schrijver, J. Gotlib, and J. L. Zehnder Design and Evaluation of a Real-Time PCR Assay for Quantification of JAK2 V617F and Wild-Type JAK2 Transcript Levels in the Clinical Laboratory J. Mol. Diagn., January 1, 2010; 12(1): 58 - 64. [Abstract] [Full Text] [PDF] Z. Ye, H. Zhan, P. Mali, S. Dowey, D. M. Williams, Y.-Y. Jang, C. V. Dang, J. L. Spivak, A. R. Moliterno, and L. 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