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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, 2004; DOI 10.1182/blood-2003-10-3661.
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and resistance to arachidonate-induced deathFrom the Graduate Institute of Medical Technology, Departments of Pathology, Internal Medicine, and Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan; Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Cardiology, Chang-Gung Memorial Hospital, Taipei, Taiwan; Vascular Biology Research Center, Institute of Molecular Medicine, and Division of Hematology, University of Texas Health Science Center, Houston, TX.
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 physiologic roles, we generated TXAS-deleted mice by gene targeting. TXAS–/– mice had normal bone marrow megakaryocytes, normal 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 prostaglandin-E2 (PGE2), PGD2, and PGF2
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
. AA infusion caused a progressive drop of mean arterial pressure (MAP), cardiac arrest, and death in wild-type (WT) mice but did not induce shock in TXAS–/– mice or in WT and TXAS–/– mice treated with antagonist to the thromboxane-prostanoid (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 pathophysiologic processes. 
