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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5323-5329. Prepublished online as a Blood First Edition Paper on December 24, 2008; DOI 10.1182/blood-2008-07-169359. This Article Full Text (PDF) All Versions of this Article: blood-2008-07-169359v1 113/21/5323    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 Banno, F. Articles by Miyata, T. Search for Related Content PubMed PubMed Citation Articles by Banno, F. Articles by Miyata, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 17, 2008 Accepted December 16, 2008 The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation Fumiaki Banno, Anil K. Chauhan, Koichi Kokame, Jin Yang, Shigeki Miyata, Denisa D. Wagner, and Toshiyuki Miyata* Research Institute, National Cardiovascular Center, Suita, Japan Immune Disease Institute, Harvard Medical School, Boston, MA, United States Division of Transfusion Medicine, National Cardiovascular Center, Suita, Japan Department of Pathology, Harvard Medical School, Boston, MA, United States * Corresponding author; email: miyata{at}ri.ncvc.go.jp. ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor (VWF). We previously identified two types of mouse Adamts13 gene: The 129/Sv-strain Adamts13 gene encodes the long form ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain Adamts13 gene encodes the short form ADAMTS13 lacking the distal C-terminal domains. To assess the physiological significance of the distal C-terminal domains of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice (Adamts13S/S) that carry the short form ADAMTS13. Similar to wild-type 129/Sv mice (Adamts13L/L), Adamts13S/S did not have ultra-large VWF multimers in plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice (Adamts13-/-). However, in vitro thrombogenesis under flow at a shear rate of 5000 s-1 was accelerated in Adamts13S/S compared to Adamts13L/L. Both in vivo thrombus formation in ferric chloride-injured arterioles and thrombocytopenia induced by collagen plus epinephrine challenge were more dramatic in Adamts13S/S than in Adamts13L/L but less than in Adamts13-/-. These results suggested that the C-terminally truncated ADAMTS13 exhibited decreased activity in the cleavage of VWF under high shear rate. Role of the C-terminal domains may become increasingly important under prothrombotic conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ADAMTS13's tail tale Karen Vanhoorelbeke, Hendrik B. Feys, and Simon F. De Meyer Blood 2009 113: 5039-5040. [Full Text] [PDF] This article has been cited by other articles: S. Zanardelli, A. C. K. Chion, E. Groot, P. J. Lenting, T. A. J. McKinnon, M. A. Laffan, M. Tseng, and D. A. Lane A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF Blood, September 24, 2009; 114(13): 2819 - 2828. [Abstract] [Full Text] [PDF] K. Vanhoorelbeke, H. B. Feys, and S. F. De Meyer ADAMTS13's tail tale Blood, May 21, 2009; 113(21): 5039 - 5040. [Full Text] [PDF]

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