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Blood, 2 July 2009, Vol. 114, No. 1, pp. 119-127. Prepublished online as a Blood First Edition Paper on March 30, 2009; DOI 10.1182/blood-2009-01-198937. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2009-01-198937v1 114/1/119    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 ter Brugge, P. J. Articles by Hendriks, R. W. Search for Related Content PubMed PubMed Citation Articles by ter Brugge, P. J. Articles by Hendriks, R. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 12, 2009 Accepted March 16, 2009 A mouse model for chronic lymphocytic leukemia based on expression of the SV40 large T antigen Petra J. ter Brugge, Van B.T. Ta, Marjolein J.W. de Bruijn, Guido Keijzers, Dik C. van Gent, and Rudi W. Hendriks* Department of Immunology, Erasmus MC, Rotterdam, Netherlands Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, Netherlands * Corresponding author; email: r.hendriks{at}erasmusmc.nl. The simian virus 40 (SV40) T antigen is a potent oncogene able to transform many cell types and has been implicated in leukemia and lymphoma. In this report, we have achieved sporadic SV40 T antigen expression in mature B cells in mice, by insertion of a SV40 T antigen gene in opposite transcriptional orientation in the immunoglobulin (Ig) heavy (H) chain locus between the D en JH segments. SV40 T antigen expression appeared to result from retention of the targeted germline allele and concomitant anti-sense transcription of SV40 large T in mature B cells, leading to chronic lymphocytic leukemia (CLL). Although B cell development was unperturbed in young mice, aging mice showed accumulation of a monoclonal B cell population in which the targeted IgH allele was in germline configuration and the wild-type IgH allele had a productive V(D)J recombination. These leukemic B cells were IgDlowCD5+ and manifested nonrandom usage of V, D, and J segments. VH regions were either unmutated, with preferential usage of the VH11 family, or manifested extensive somatic hypermutation. Our findings provide an animal model for B-CLL and show that pathways activated by SV40 T antigen play important roles in the pathogenesis of B-CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mighty mouse Amy J. Johnson Blood 2009 114: 3. [Abstract] [Full Text] [PDF] This article has been cited by other articles: A. J. Johnson Mighty mouse Blood, July 2, 2009; 114(1): 3 - 3. [Abstract] [Full Text] [PDF]

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