Previously, we generated thymic lymphoma cell lines from EβR/Rp53−/− (EP) double mutant mice where the T cell receptor (TCR) β enhancer (Eβ) was deleted, and the p53 gene was inactivated. Here, we characterized the EP cell lines to study the roles of the Eβ and p53 on TCRβ rearrangements during lymphomagenesis. Recombination activation genes (RAGs) were expressed, while the TCRβ chain was not expressed in the EP cell lines. Dβ-Jβ rearrangements were not detected at all, and Dβ1 and Dβ2 cleavages were also not detected in the EP cell lines. However, Jβ cleavages suppressed in Eβ mutant thymocytes were readily detected in the EP cell lines. The Jβ cleavages appeared to be uncoupled, aberrant, RAG-dependent and Eβ-independent and were not detected in a p53 or Eβ single mutant background, suggesting that the Jβ cleavages are selected in the Eβ and p53 double mutant background. Sequence analysis showed that the cleavage occurred in the cryptic recombination signal sequences (RSSs) present throughout Jβ gene segments. The results implicate that the uncoupled and aberrant V(D)J cleavages may contribute to double-strand break-mediated genome instability during lymphomagenesis in EP mice.

Related Articles