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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1733-1739. Prepublished online as a Blood First Edition Paper on June 3, 2004; DOI 10.1182/blood-2004-01-0138. This Article Full Text (PDF) All Versions of this Article: 2004-01-0138v1 104/6/1733    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 Jin, D.-Y. Articles by Monahan, P. E Search for Related Content PubMed PubMed Citation Articles by Jin, D.-Y. Articles by Monahan, P. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 13, 2004 Accepted May 4, 2004 Creation of a mouse expressing defective human factor IX Da-Yun Jin, Tai-Ping Zhang, Tong Gui, Darrel W Stafford*, and Paul E Monahan Biology, UNC Chapel Hill, Chapel Hill, NC, USA Pediatrics, UNC Chapel Hill, Chapel Hill, NC, USA; Gene Therapy, UNC Chapel Hill, Chapel Hill, NC, USA * Corresponding author; email: dws{at}email.unc.edu. The majority of cases of human hemophilia B are the result of missense mutations in the coagulation factor IX gene, and defective circulating factor IX is detectable in most patients. The available mouse factor IX knockout models of hemophilia B (FIXKO mouse) reproduce the bleeding phenotype of human hemophilia B, but because they produce no factor IX they fail to reproduce the dominant human phenotype. We have created a human factor IX mouse model of hemophilia B (R333Q-hFIX mouse) by homologous recombination in embryonic stem cells. The mouse expresses no mouse factor IX, but instead expresses a missense mutant human factor IX from the mouse FIX promoter. Mutant human factor IX mRNA transcript and circulating human factor IX are detectable throughout development, but factor IX activity is <1% and the mouse exhibits the hemophilic phenotype. When R333Q-hFIX mice were challenged by intramuscular injection of adeno-associated virus expressing human factor IX, factor IX expression without the development of antibodies was observed. In contrast, given the same treatment, FIXKO mice consistently develop antibodies. Our R333Q-hFIX mice strain will complement the FIXKO mice for studying the kinetics of circulating factor IX circulating and gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A more clinically relevant mouse model of hemophilia B Katherine Parker Ponder Blood 2004 104: 1595. [Full Text] [PDF] This article has been cited by other articles: J. Sun, N. Hakobyan, L. A. Valentino, B. L. Feldman, R. J. Samulski, and P. E. Monahan Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX Blood, December 1, 2008; 112(12): 4532 - 4541. [Abstract] [Full Text] [PDF] S. Burns, G. O. Cory, W. Vainchenker, and A. J. Thrasher Mechanisms of WASp-mediated hematologic and immunologic disease Blood, December 1, 2004; 104(12): 3454 - 3462. [Abstract] [Full Text] [PDF]

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