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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3061-3067. Prepublished online as a Blood First Edition Paper on July 27, 2006; DOI 10.1182/blood-2006-04-014688. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-04-014688v1 108/9/3061    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 Lemmerhirt, H. L. Articles by Ginsburg, D. Search for Related Content PubMed PubMed Citation Articles by Lemmerhirt, H. L. Articles by Ginsburg, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf gene Heidi L. Lemmerhirt, Jordan A. Shavit, Gallia G. Levy, Suzanne M. Cole, Jeffrey C. Long, and David Ginsburg From the Departments of Human Genetics, Internal Medicine, and Pediatrics, the Cellular and Molecular Biology Program, the Life Sciences Institute, and the Howard Hughes Medical Institute, the University of Michigan, Ann Arbor, MI. Both genetic and environmental influences contribute to the wide variation in plasma von Willebrand factor (VWF) levels observed in humans. Inbred mouse strains also have highly variable plasma VWF levels, providing a convenient model in which to study genetic modifiers of VWF. Previously, we identified a major modifier of VWF levels in the mouse (Mvwf1) as a regulatory mutation in murine Galgt2. We now report the identification of an additional murine VWF modifier (Mvwf2). Mvwf2 accounts for approximately 16% of the 8-fold plasma VWF variation (or 25% of the genetic variation) observed between the A/J and CASA/RkJ strains and maps to the murine Vwf gene itself. Twenty SNPs were identified within the coding regions of the A/J and CASA/RkJ Vwf alleles, and in vitro analysis of recombinant VWF demonstrated that a single SNP (+7970G>A) and the associated nonsynonymous amino acid change (R2657Q) confers a significant increase in VWF biosynthesis from the CASA/RkJ Vwf allele. This change appears to represent a unique gain of function that likely explains the mechanism of Mvwf2 in vivo. The identification of a natural Vwf gene variant among inbred mice affecting biosynthesis suggests that similar genetic variation may contribute to the wide range of VWF levels observed in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mouse VWF again teaches us diversity of mechanisms Robert R. Montgomery Blood 2006 108: 2887. [Full Text] [PDF] This article has been cited by other articles: J. M. Johnsen, M. Teschke, P. Pavlidis, B. M. McGee, D. Tautz, D. Ginsburg, and J. F. Baines Selection on cis-Regulatory Variation at B4galnt2 and Its Influence on von Willebrand Factor in House Mice Mol. Biol. Evol., March 1, 2009; 26(3): 567 - 578. [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]

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