| First Author | ter Brugge PJ | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 1 | Pages | 119-27 |
| PubMed ID | 19332766 | Mgi Jnum | J:150315 |
| Mgi Id | MGI:3850306 | Doi | 10.1182/blood-2009-01-198937 |
| Citation | ter Brugge PJ, et al. (2009) A mouse model for chronic lymphocytic leukemia based on expression of the SV40 large T antigen. Blood 114(1):119-27 |
| abstractText | 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 and J(H) segments. SV40 T-antigen expression appeared to result from retention of the targeted germline allele and concomitant antisense 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 IgD(low)CD5(+) and manifested nonrandom usage of V, D, and J segments. V(H) 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. |
