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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1266-1273. Prepublished online as a Blood First Edition Paper on November 8, 2007; DOI 10.1182/blood-2007-09-111369. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-111369v1 111/3/1266    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 CrossRef Google Scholar Articles by Cheli, Y. Articles by Kunicki, T. J. PubMed PubMed Citation Articles by Cheli, Y. Articles by Kunicki, T. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6–/– mice Yann Cheli1, Deborah Jensen2, Patrizia Marchese1, David Habart1, Tim Wiltshire2, Michael Cooke2, José A. Fernandez1, Jerry Ware1, Zaverio M. Ruggeri1, and Thomas J. Kunicki1 1 Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; and 2 Genomics Institute of the Novartis Research Foundation, San Diego, CA Platelet glycoprotein VI (GPVI) is a key receptor for collagens that mediates the propagation of platelet attachment and activation. Targeted disruption of the murine gene Gp6 on a mixed 129 x 1/SvJ x C57BL/6J background causes the expected defects in collagen-dependent platelet responses in vitro. The extent of this dysfunction in all Gp6–/– mice is uniform and is not affected by genetic background. However, the same Gp6–/– mice exhibit 2 diametrically opposed phenotypes in vivo. In some mice, tail bleeding times are extremely prolonged, and thrombus formation in an in vivo carotid artery ferric chloride-injury model is significantly impaired. In other littermates, tail bleeding times are within the range of wild-type mice, and in vivo thrombus formation is indistinguishable from that of control mice. Directed intercrosses revealed that these phenotypes are heritable, and a genome-wide single-nucleotide polymorphism scan revealed the most significant linkage to a single locus (8 megabases) on chromosome 4 (logarithm of the odds [LOD] score = 6.9, P < .0001) that we designate Modifier of hemostasis (Mh). Our results indicate that one or more modifier genes in Mh control the extent to which in vivo platelet thrombus formation is disrupted by the absence of platelet GPVI. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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