抄録
We have identified two pathways for the 5' deletion of Notch1 gene in radiation-induced thymic lymphomas; illegitimate V(D)J recombination in wild-type mice and microhomology-mediated nonhomologous end-joining (MNHEJ) in scid mice. We report that there are Rag2-dependent and Rag2-independet pathways for the induction of thymic lymphomas. The wild-type C.B-17 mice exhibited no induction of thymic lymphomas by 2 Gy gamma-irradiation, while Rag2-/-, scid, and Rag2-/- scid mice all displayed high frequencies of radiation-induced thymic lymphomas. This indicates that there is a Rag2-independent pathway for induction of thymic lymphomas. Notch1 abnormalities were induced by irradiation at high frequencies in these mice, suggesting that there is a Rag2-independent pathway for induction of Notch1 abnormality. In wild-type mice, the 5' deletions of Notch1 were formed via illegitimate V(D)J recombination and those in scid mice were formed via illegitimate V(D)J recombination and MNHEJ. In contrast, in Rag2-/- or Rag2-/- scid mice, the 5' deletions were formed via MNHEJ. These results indicate that in the presence of Rag2 gene, Rag2-dependent illegitimate V(D)J recombination functions as a main mechanism for the deletion formation, while in the absence of Rag2 gene, Rag2-independent MNHEJ works mainly in the deletion formation. The 5' deletions formed via Rag2-dependent illegitimate V(D)J recombination occur spontaneously in wild-type thymocytes.
