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 p53 is known to be required for the induction of apoptosis in thymocytes following DNA damage. To examine whether the development of thymic lymphoma in p53-/- mice was dependent on the process of V(D)J recombination, we generated p53-/- mice that were also mutant for the Rag1 or Rag2 genes. Both Rag1-/-; p53-/- and Rag2-/-; p53-/- mice developed thymic lymphoma at high frequency, and the tumors arose with short latency. Interestingly, the thymic tumors were composed of CD4+CD8+ cells, although there was no evidence for normal V(D)J recombination. These data suggest that normal V(D)J recombination is not required for the development of thymic lymphoma in the context of a p53 germ-line mutation.
Nacht
M
M
Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Jacks
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte; D016654:Genes, RAG-1; D016158:Genes, p53; D018095:Germ-Line Mutation; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases