Transgenic Expression of A238L, a Virus Host Modification Protein, in mouse T cells

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 metastatic, angiogenic and transplantable CD4+CD8+ CD69- lymphoma. 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, mutA238L, solely inhibiting transcription mediated by NFkappaB, were indistinguishable from wild type mice. Expression of Rag 1, Rag2, TCRbeta V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1, 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. Purified CD4+CD8+CD69- thymocytes were prepared for wild-type control FVB/N mice, as well as from the FVB/N transgenic mice expressing the A238L and the mutated A238L, mutA238L. Comparisons were performed between the two transgenic mice lines and the control mice.