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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 5, 2006 Accepted June 25, 2006 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* The University of Michigan, Ann Arbor, MI, USA * Corresponding author; email: ginsburg{at}umich.edu. 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 ~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 non-synonymous 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: 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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