Abstract
We have previously identified two pathways for the deletion formation of Notch1 gene in radiation-induced mouse thymic lymphomas: in wild-type mice, the 5' deletion of Notch1 was induced by illegitimate V(D)J recombination using recombination signal sequence-like elements present in the 5' region of Notch1, whereas in the absence of DNA-PKcs function in scid mice, microhomology-mediated end-joining pathway acts as a mechanism for deletion formation. While it was reported that there was no induction of thymic lymphoma by radiation in scid mice without Rag gene, we demonstrated that even in the absence of Rag2 gene, scid mice developed rediation-induced thymic lymphomas, which is consistent with the notion that there are two pathways in the deletion formation. To validate the presence of two pathways, the Notch1 abnormalities in radiation-induced thymic lymphomas developed in Rag2-KO, scid, and Rag2-KOscid mice were examined by Southern blot hybridization. The results showed that in the absence of Rag2 gene, the 5' deletions were formed, demonstrating that there is a Rag-independent deletion pathway. [J Radiat Res 44:398 (2003)]
