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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1274-1281. Prepublished online as a Blood First Edition Paper on November 13, 2007; DOI 10.1182/blood-2007-06-092338. This Article Full Text (PDF) All Versions of this Article: blood-2007-06-092338v1 111/3/1274    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Merkulov, S. Articles by McCrae, K. R Search for Related Content PubMed PubMed Citation Articles by Merkulov, S. Articles by McCrae, K. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2007 Accepted October 29, 2007 Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis Sergei Merkulov, Wan-Ming Zhang, Anton A Komar, Alvin H Schmaier, Ellen Barnes, Yihua Zhou, Xincheng Lu, Takayuki Iwaki, Francis J Castellino, Guangbin Luo, and Keith R McCrae* Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States Department of Biological, Geological & Environmental Science, Cleveland State University, Cleveland, OH, United States Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH, United States W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, United States * Corresponding author; email: keith.mccrae{at}case.edu. High molecular weight kininogen (HK) plays an important role in the assembly of the plasma kallikrein-kinin system. While the human genome contains a single copy of the kininogen gene, three copies exist in the rat (one encoding K-kininogen and two encoding T-kininogen). Here, we confirm that the mouse genome contains two homologous kininogen genes, mKng1 and mKng2, and demonstrate that these genes are expressed in a tissue-specific manner. To determine the roles of these genes in murine development and physiology, we disrupted mKng1, which is expressed primarily in the liver. mKng1-/- mice were viable, but lacked plasma HK and low molecular weight kininogen (LK), as well as mHK-D5, a novel kininogen isoform that lacks kininogen domain 5. Moreover, despite normal tail vein bleeding times, mKng1-/- mice displayed a significantly prolonged time to carotid artery occlusion following Rose Bengal administration and laser induced arterial injury. These results suggest that a single gene, mKng1, is responsible for production of plasma kininogen, and that plasma high molecular weight kininogen contributes to induced arterial thrombosis in mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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