V(D)J RECOMBINATION IS NOT REQUIRED FOR THE DEVELOPMENT OF LYMPHOMA IN P53-DEFICIENT MICE

The most common tumor in p53-deficient mice is thymic lymphoma, and p5 3 is known to be required for the induction of apoptosis in thymocytes following DNA damage. To examine whether the development of thymic ly mphoma in p53(-/-) mice was dependent on the process of V(D)J recombin ation, we generated p53(-/-) mice that were also mutant for the Rag1 o r Rag2 genes. Both Rag1(-/-); p53(-/-) and Rag2(-/-); p53(-/-) mice de veloped thymic lymphoma at high frequency, and the tumors arose with s hort latency. Interestingly, the thymic tumors were composed of CD4(+) CD8(+) cells, although there was no evidence for normal V(D)J recombin ation. These data suggest that normal V(D)J recombination is not requi red for the development of thymic lymphoma in the context of a p53 ger m-line mutation.