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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2339-2344. Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2004-03-1127. This Article Full Text (PDF) All Versions of this Article: 2004-03-1127v1 104/8/2339    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 Kato, K. Articles by Ware, J. Search for Related Content PubMed PubMed Citation Articles by Kato, K. Articles by Ware, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 24, 2004 Accepted May 18, 2004 Genetic deletion of mouse platelet glycoprotein Ib produces a Bernard-Soulier phenotype with increased -granule size Kazunobu Kato, Constantino Martinez, Susan Russell, Paquita Nurden, Alan Nurden, Steven Fiering, and Jerry Ware* Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA UMR5533 CNRS Hopital Cardiologique, Pessac, France Department of Microbiology and Immunology, Dartmouth-Hitchcock Medical School, Lebanon, NH, USA * Corresponding author; email: jware{at}scripps.edu. Here we report the characterization of a mouse model of the Bernard-Soulier syndrome generated by a targeted disruption of the gene encoding the glycoprotein (GP) Ib subunit of the GP Ib-IX complex. Similar to a Bernard-Soulier model generated by disruption of the mouse GP Ib subunit, GP IbNull mice display macrothrombocytopenia and a severe bleeding phenotype. When examined by transmission electron microscopy, the large platelets produced by a GP IbNull genotype revealed -granules with increased size as compared to the -granules from control mouse platelets. Data is presented linking the over expression of a septin protein, SEPT5, to the presence of larger -granules in the GP IbNull platelet. The SEPT5 gene resides approximately 250 nucleotides 5' to the GP Ib gene and has been associated with modulating exocytosis from neurons and platelets as part of a presynaptic protein complex. Fusion mRNA transcripts present in megakaryocytes can contain both the SEPT5 and GP Ib coding sequences as a result in an imperfect polyadenylation signal within the 3' end of both the human and mouse SEPT5 genes. We observed a 2-3 fold increase in SEPT5 protein levels in platelets from GP IbNull mice. These results implicate SEPT5 levels in the maintenance of normal -granule size and may explain the variant granules associated with human GP Ib mutations and the Bernard-Soulier syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. E. Geddis The regulation of proplatelet production Haematologica, June 1, 2009; 94(6): 756 - 759. [Full Text] [PDF] C. Strassel, A. Eckly, C. Leon, C. Petitjean, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome Haematologica, June 1, 2009; 94(6): 800 - 810. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. Nieswandt Cell Adhesion Mechanisms in Platelets Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 403 - 412. [Abstract] [Full Text] [PDF] U. J.H. Sachs and B. Nieswandt In Vivo Thrombus Formation in Murine Models Circ. Res., April 13, 2007; 100(7): 979 - 991. [Abstract] [Full Text] [PDF] C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF] C. Strassel, C. Nonne, A. Eckly, T. David, C. Leon, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Decreased Thrombotic Tendency in Mouse Models of the Bernard-Soulier Syndrome Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 241 - 247. [Abstract] [Full Text] [PDF] B. Lo, L. Li, P. Gissen, H. Christensen, P. J. McKiernan, C. Ye, M. Abdelhaleem, J. A. Hayes, M. D. Williams, D. Chitayat, et al. Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet {alpha}-granule biogenesis Blood, December 15, 2005; 106(13): 4159 - 4166. [Abstract] [Full Text] [PDF] T. Rabie, A. Strehl, A. Ludwig, and B. Nieswandt Evidence for a Role of ADAM17 (TACE) in the Regulation of Platelet Glycoprotein V J. Biol. Chem., April 15, 2005; 280(15): 14462 - 14468. [Abstract] [Full Text] [PDF] C. Martinez and J. Ware Mammalian Septin Function in Hemostasis and Beyond Experimental Biology and Medicine, December 1, 2004; 229(11): 1111 - 1119. [Abstract] [Full Text] [PDF]

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