| First Author | Almeida SC | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 4 | Pages | e34140 |
| PubMed ID | 22558084 | Mgi Jnum | J:187185 |
| Mgi Id | MGI:5435646 | Doi | 10.1371/journal.pone.0034140 |
| Citation | Almeida SC, et al. (2012) Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein. PLoS One 7(4):e34140 |
| abstractText | Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-kappaB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4(+)CD8(+)CD69(-) lymphoma. The CD4(+)CD8(+)CD69(-) cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-kappaB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRbeta-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4(+)CD8(+)CD69(-) thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4(+)CD8(+) CD69(-) thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas. |
