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This Article Full Text Full Text (PDF) 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 Cui, J. Articles by Ginsburg, D. Search for Related Content PubMed PubMed Citation Articles by Cui, J. Articles by Ginsburg, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2000, Vol. 96, No. 13, pp. 4222-4226 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Spontaneous thrombosis in mice carrying the factor V Leiden mutation Jisong Cui, Daniel T. Eitzman, Randal J. Westrick, Patricia D. Christie, Zuojun J. Xu, Angela Y. Yang, Anjali A. Purkayastha, Tony L. Yang, Alan L. Metz, Kim P. Gallagher, Julia A. Tyson, Robert D. Rosenberg, and David Ginsburg From the Divisions of Medical Genetics and Cardiology, Department of Internal Medicine, Department of Human Genetics, and the Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor MI; Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co, Ann Arbor, MI; and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. A polymorphism in coagulation factor V, factor V Leiden (FVL), is the major known genetic risk factor for thrombosis in humans. Approximately 10% of mutation carriers experience clinically significant thrombosis in their lifetime. In a small subset of patients, thrombosis is associated with coinheritance of other prothrombotic gene mutations. However, the potential contribution of additional genetic risk factors in the majority of patients remains unknown. To gain insight into the molecular basis for the variable expressivity of FVL, mice were generated carrying the homologous mutation (R504Q [single-letter amino acid codes]) inserted into the endogenous murine Fv gene. Adult heterozygous (FvQ/+) and homozygous (FvQ/Q) mice are viable and fertile and exhibit normal survival. Compared with wild-type mice, adult FvQ/Q mice demonstrate a marked increase in spontaneous tissue fibrin deposition. No differences in fetal development or survival are observed among FvQ/Q, FvQ/+ or control littermates on the C57BL/6J genetic background. In contrast, on a mixed 129Sv-C57BL/6J genetic background, FvQ/Q mice develop disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. These results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within FV among mammalian species and suggest an important contribution of other genetic factors to the thrombosis associated with FVL in humans. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Kisucka, A. K. Chauhan, B.-Q. Zhao, I. S. Patten, A. Yesilaltay, M. Krieger, and D. D. Wagner Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis Blood, June 4, 2009; 113(23): 6015 - 6022. [Abstract] [Full Text] [PDF] F. Banno, A. K. Chauhan, K. Kokame, J. Yang, S. Miyata, D. D. Wagner, and T. Miyata The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation Blood, May 21, 2009; 113(21): 5323 - 5329. [Abstract] [Full Text] [PDF] H. 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