| First Author | Jacobs H | Year | 1996 |
| Journal | Oncogene | Volume | 12 |
| Issue | 10 | Pages | 2089-99 |
| PubMed ID | 8668334 | Mgi Jnum | J:33416 |
| Mgi Id | MGI:80896 | Citation | Jacobs H, et al. (1996) Oncogenic potential of a pre-T cell receptor lacking the TCR beta variable domain. Oncogene 12(10):2089-99 |
| abstractText | In transgenic mice expressing a mutated T cell receptor (TCR) beta chain lacking the variable domain (DeltaV-TCRbeta) T cell differentiation is arrested at the CD4+ CD8+ thymocyte stage. Here, we report that these transgenic animals develop CD4+, CD8+, IL-2 receptor alpha-positive T cell lymphomas at a very high incidence. Introduction of a normal TCRbeta gene into the DeltaV-TCRbeta transgenic mice drastically reduces the tumor incidence, while crossing the DeltaV-TCRbeta transgene onto a recombinase-deficient RAG-1-/- background does not prevent tumor development. Therefore, the induction of T cell lymphomas is a property of the mutated TCRbeta chain. The DeltaV-TCRbeta chain appears at the cell surface as a disulfide-linked DeltaV-TCRbeta/pTalpha dimer in association with CD3gamma and -episilon, but not with CD3delta. This mutated preTCR/CD3 complex is shown to induce pre-T cell proliferation and differentiation, but does not permit formation of a normally sized CD4+8+ thymic compartment. DeltaV-TCRbeta transgenic mice frequently show an expansion of CD4+8+, IL-2 receptor alpha+ pre-T cells early in life. These cells likely represent the population that is subject to oncogenic transformation. |
