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Blood, 15 January 2009, Vol. 113, No. 3, pp. 696-704. Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-07-169003. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-169003v1 113/3/696    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 Citing Articles via Google Scholar Google Scholar Articles by Mullins, E. S. Articles by Degen, J. L. Search for Related Content PubMed PubMed Citation Articles by Mullins, E. S. Articles by Degen, J. L. Related Collections Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain Eric S. Mullins1, Keith W. Kombrinck2, Kathryn E. Talmage2, Maureen A. Shaw1, David P. Witte3, Joni M. Ullman4, Sandra J. Degen2, William Sun2, Matthew J. Flick5, and Jay L. Degen3 Divisions of 1 Pediatric Hematology/Oncology, 3 Developmental Biology, 3 Pathology, 4 Immunobiology, and 5 Rheumatology, Cincinnati Children's Hospital Research Foundation and University of Cincinnati College of Medicine, OH Mice carrying a conditional prothrombin knockout allele (fIIlox) were established to develop an experimental setting for exploring the importance of thrombin in the maintenance of vascular integrity, the inflammatory response, and disease processes in adult animals. In the absence of Cre-mediated recombination, homozygous fIIlox/lox mice or compound heterozygous mice carrying one fIIlox allele and one constitutive-null allele were viable. Young adults exhibited neither spontaneous bleeding events nor diminished reproductive success. However, the induction of Cre recombinase in fIIlox mice using the poly I:C-inducible Mx1-Cre system resulted in the rapid and near-complete recombination of the fIIlox allele within the liver, the loss of circulating prothrombin, and profound derangements in coagulation function. Consistent with the notion that thrombin regulates coagulation and inflammatory pathways, an additional early consequence of reducing prothrombin was impaired antimicrobial function in mice challenged with Staphylococcus aureus peritonitis. However, life expectancy in unchallenged adults genetically depleted of prothrombin was very short (5-7 days). The loss of viability was associated with the development of severe hemorrhagic events within multiple tissues, particularly in the heart and brain. Unlike the constitutive loss of either clotting or platelet function alone, the conditional loss of prothrombin is uniformly not compatible with maintenance of hemostasis or long-term survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Bleeding hearts Nigel Mackman Blood 2009 113: 500-501. [Full Text] [PDF]

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