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Blood, 1 July 2004, Vol. 104, No. 1, pp. 135-142. Prepublished online as a Blood First Edition Paper on March 16, 2004March 9, 2004; DOI 10.1182/blood-2003-10-3661. This Article Full Text (PDF) All Versions of this Article: 2003-10-3661v1 2003-10-3661v2 104/1/135    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 Yu, I-S. Articles by Lin, S.-W. Search for Related Content PubMed PubMed Citation Articles by Yu, I-S. Articles by Lin, S.-W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 28, 2003 Accepted February 26, 2004 TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis and resistance to arachidonate-induced death I-Shing Yu, Shu-Rung Lin, Chin-Chin Huang, Hui-Yu Tseng, Pei-Hsing Huang, Guey-Yueh Shi, Hwa-Lin Wu, Chi-Luh Tang, Pao-Hsien Chu, Lee-Ho Wang, Kenneth K Wu, and Shu-Wha Lin* Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan Department of Pathology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan Division of Cardiology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan Vascular Biology Research Center, Institute of Molecular Medicine, and Division of Hematology, University of Texas Health Science Center, Houston, TX, USA Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan * Corresponding author; email: mtshuwha{at}ccms.ntu.edu.tw. Besides its well-recognized role in hemostasis and thrombosis, thromboxane A2 synthase (TXAS) is proposed to be involved in thrombopoiesis and lymphocyte differentiation. To evaluate its various physiological roles, we generated TXAS-deleted mice by gene targeting. TXAS-/- mice had normal bone marrow megakaryocytes, blood platelet counts, and normal CD4 and CD8 lymphocyte counts in thymus and spleen. Platelets from TXAS-/- mice failed to aggregate or generate thromboxane B2 in response to arachidonic acid (AA) but produced increased PGE2, PGD2 and PGF2. AA infusion caused a progressive drop of mean arterial pressure (MAP), cardiac arrest and death in WT mice, but did not induce shock in TXAS-/-TXAS-/- mice, nor in WT and TXAS-/- mice treated with antagonist to the TP receptor. The TXAS-/- mice were able to maintain normal MAP upon AA insult when TP was present but were unable to do so when TP was blocked by an antagonist, suggesting a role of endoperoxide accumulation in influencing MAP. We conclude that TXAS is not essential for thrombopoiesis and lymphocyte differentiation. Its deficiency causes a mild hemostatic defect and protects mice against arachidonate-induced shock and death. The TXAS-deleted mice will be valuable for investigating the roles of arachidonate metabolic shunt in various pathophysiological processes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-H. Lin, Y.-M. Lin, Y.-Y. Wang, I-S. Yu, Y.-W. Lin, Y.-H. Wang, C.-M. Wu, H.-A. Pan, S.-C. Chao, P. H. Yen, et al. The Expression Level of Septin12 Is Critical for Spermiogenesis Am. J. Pathol., May 1, 2009; 174(5): 1857 - 1868. [Abstract] [Full Text] [PDF] A. W. Ashton, S. Mukherjee, F. Nagajyothi, H. Huang, V. L. Braunstein, M. S. Desruisseaux, S. M. Factor, L. Lopez, J. W. Berman, M. Wittner, et al. Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection J. Exp. Med., April 16, 2007; 204(4): 929 - 940. [Abstract] [Full Text] [PDF] K.-Y. Su, W.-L. Chien, W.-M. Fu, I-S. Yu, H.-P. Huang, P.-H. Huang, S.-R. Lin, J.-Y. Shih, Y.-L. Lin, Y.-P. Hsueh, et al. Mice Deficient in Collapsin Response Mediator Protein-1 Exhibit Impaired Long-Term Potentiation and Impaired Spatial Learning and Memory J. Neurosci., March 7, 2007; 27(10): 2513 - 2524. [Abstract] [Full Text] [PDF] S Moncada Adventures in vascular biology: a tale of two mediators Phil Trans R Soc B, May 29, 2006; 361(1469): 735 - 759. [Abstract] [Full Text] [PDF]

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