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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1054-1062. Prepublished online as a Blood First Edition Paper on April 14, 2005; DOI 10.1182/blood-2004-08-3306. This Article Full Text (PDF) All Versions of this Article: 2004-08-3306v1 106/3/1054    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 Wiesner, S. M Articles by Largaespada, D. A Search for Related Content PubMed PubMed Citation Articles by Wiesner, S. M Articles by Largaespada, D. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2004 Accepted April 9, 2005 A repressible transgenic model of NRAS oncogene driven mast cell disease in the mouse Stephen M Wiesner, Jamie M Jones, Diane E Hasz, and David A Largaespada* University of Minnesota Comprehensive Cancer Center, Minneapolis, MN, USA * Corresponding author; email: larga002{at}umn.edu. In an effort to create a model in which to study the effects of RAS dysregulation in hematopoietic disease, we have developed separate founder lines of transgenic mice with the tetracycline transactivator (tTA) driven by the Vav hematopoietic promoter in one line, and NRASV12 driven by the tetracycline responsive element (TRE2) in the other. When these lines are crossed, doubly transgenic animals uniformly develop a disease similar to human Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia (MCL) between two and four months of age. Disease is characterized by tissue infiltrates of large, well differentiated mast cells in the spleen, liver, skin, lung and thymus. Analysis of bone sections show small to large foci of similarly well differentiated mast cells. Results also show that transgene expression and this disease are repressible by administration of doxycycline in the drinking water of affected animals. These results indicate that NRASV12 expression is required to initiate and maintain disease in this model. This inducible system of transgenes, developed as a model of mutant NRASV12 oncogene driven myeloid disease, will be useful for studying the role of RAS dysregulation in hematopoietic disease in general, as well as discrete human diseases, specifically ASM and MCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W.-I. Kim, I. Matise, M. D. Diers, and D. A. Largaespada RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia Blood, January 29, 2009; 113(5): 1086 - 1096. [Abstract] [Full Text] [PDF] N. Omidvar, S. Kogan, S. Beurlet, C. le Pogam, A. Janin, R. West, M.-E. Noguera, M. Reboul, A. Soulie, C. Leboeuf, et al. BCL-2 and Mutant NRAS Interact Physically and Functionally in a Mouse Model of Progressive Myelodysplasia Cancer Res., December 15, 2007; 67(24): 11657 - 11667. [Abstract] [Full Text] [PDF] C. Parikh, R. Subrahmanyam, and R. Ren Oncogenic NRAS rapidly and efficiently induces CMML- and AML-like diseases in mice Blood, October 1, 2006; 108(7): 2349 - 2357. [Abstract] [Full Text] [PDF]

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