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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2767-2774. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-03-1028. This Article Full Text (PDF) All Versions of this Article: 2004-03-1028v1 104/9/2767    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 Sabatino*, D. E Articles by High, K. A Search for Related Content PubMed PubMed Citation Articles by Sabatino*, D. E Articles by High, K. A Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 18, 2004 Accepted June 18, 2004 Novel Hemophilia B Mouse Models Exhibiting a Range of Mutations in the Factor IX Gene Denise E Sabatino*, Elina Armstrong*, Shyrie Edmonson, Yi-Lin Liu, Marc Pleimes, Joerg Schuettrumpf, Julie Fitzgerald, Roland W Herzog, Valder R Arruda, and Katherine A High* * Corresponding author; email: high{at}email.chop.edu. Animal models have been critical to the development of novel therapeutics in hemophilia. A deficiency of current murine models of hemophilia B is that they are all due to gene deletions, a type of mutation that is relatively rare in the human hemophilia population. We generated mice with a range of mutations in the Factor IX (F.IX) gene; these more faithfully reflect the types of mutations that cause disease in the human population. Transgenic mice expressing either wild-type human F.IX (hF.IX), or F.IX variants with premature translation termination codons, or missense mutations, under the control of the murine transthyretin promoter, were generated and crossed with mice carrying a large deletion of the murine F.IX gene. Gene copy number, F.IX transcript levels in the liver, intrahepatocyte protein expression, and circulating levels of F.IX protein in the mice were determined and compared to data generated by transient transfection assays using the same F.IX variants. Mice were injected with a viral vector expressing hF.IX and displayed a range of immune responses to the transgene product, depending on the underlying mutation. These new mouse models faithfully mimic the mutations causing human disease, and will prove useful for testing novel therapies for hemophilia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Testing novel hemophilia therapies: of mice and men David Lillicrap Blood 2004 104: 2614-2615. [Full Text] [PDF] This article has been cited by other articles: Y.-L. Liu, P. Margaritis, F. Khazi, H. Downey, S. Kadauke, N. Hasbrouck, J. Sheedy, E. Welch, M. Weetall, and K. A. High Nonsense Suppression Approaches in Treating Hemophilia Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 512 - 512. [Abstract] C. Yang, J. Feng, W. Song, J. Wang, B. Tsai, Y. Zhang, W. A. Scaringe, K. A. Hill, P. Margaritis, K. A. High, et al. A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin PNAS, September 25, 2007; 104(39): 15394 - 15399. [Abstract] [Full Text] [PDF] E. Dobrzynski, J. C. Fitzgerald, O. Cao, F. Mingozzi, L. Wang, and R. W. Herzog Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells PNAS, March 21, 2006; 103(12): 4592 - 4597. [Abstract] [Full Text] [PDF] J. Schuettrumpf, R. W. Herzog, A. Schlachterman, A. Kaufhold, D. W. Stafford, and V. R. Arruda Factor IX variants improve gene therapy efficacy for hemophilia B Blood, March 15, 2005; 105(6): 2316 - 2323. [Abstract] [Full Text] [PDF]

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