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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3161-3166. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-07-2765. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2765v1 107/8/3161    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Banno, F. Articles by Miyata, T. Search for Related Content PubMed PubMed Citation Articles by Banno, F. Articles by Miyata, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura Fumiaki Banno, Koichi Kokame, Tomohiko Okuda, Shigenori Honda, Shigeki Miyata, Hisashi Kato, Yoshiaki Tomiyama, and Toshiyuki Miyata From the Research Institute and Division of Transfusion Medicine, National Cardiovascular Center, Suita, Osaka, Japan; and Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers. In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. In this study, we report characterization of mice bearing a targeted disruption of the Adamts13 gene. ADAMTS13-deficient mice were born in the expected mendelian distribution; homozygous mice were viable and fertile. Hematologic and histologic analyses failed to detect any evidence of thrombocytopenia, hemolytic anemia, or microvascular thrombosis. However, unusually large VWF multimers were observed in plasma of homozygotes. Thrombus formation on immobilized collagen under flow was significantly elevated in homozygotes in comparison with wild-type mice. Thrombocytopenia was more severely induced in homozygotes than in wild-type mice after intravenous injection of a mixture of collagen and epinephrine. Thus, a complete lack of ADAMTS13 in mice was a prothrombotic state, but it alone was not sufficient to cause TTP-like symptoms. The phenotypic differences of ADAMTS13 deficiencies between humans and mice may reflect differences in hemostatic system functioning in these species. Alternatively, factors in addition to ADAMTS13 deficiency may be necessary for development of TTP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-C. Chung, T. G. Popova, S. C. Jorgensen, L. Dong, V. Chandhoke, C. L. Bailey, and S. G. Popov Degradation of Circulating von Willebrand Factor and Its Regulator ADAMTS13 Implicates Secreted Bacillus anthracis Metalloproteases in Anthrax Consumptive Coagulopathy J. Biol. Chem., April 11, 2008; 283(15): 9531 - 9542. [Abstract] [Full Text] [PDF] A. K. Chauhan, M. T. Walsh, G. Zhu, D. Ginsburg, D. D. Wagner, and D. G. 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Motto Thrombotic Thrombocytopenic Purpura in Humans and Mice Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1901 - 1908. [Abstract] [Full Text] [PDF] W. Zhou, E. E. Bouhassira, and H.-M. Tsai An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers Blood, August 1, 2007; 110(3): 886 - 893. [Abstract] [Full Text] [PDF] K. K. Swisher, J. T. Doan, S. K. Vesely, H. C. Kwaan, B. Kim, B. Lammle, J. A. Kremer Hovinga, and J. N. George Pancreatitis preceding acute episodes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: report of five patients with a systematic review of published reports Haematologica, July 1, 2007; 92(7): 936 - 943. [Abstract] [Full Text] [PDF]

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