Mutations in thep53andScidGenes Do Not Cooperate in Lymphomagenesis in Doubly Heterozygous Mice

Analysis of double mutant mice of thep53andscidgenes, which have a combination of cell cycle checkpoint/apoptosis and DNA repair defects, shows that the latter defect synergistically enhances lymphoma development with loss of the former function. These mice lack the ability to eliminate lymphocytes predisposed to neoplastic transformation resulting from faulty antigen receptor gene rearrangement. Here we examine the cooperativity in double heterozygotes ofp53andscidin which normal development of lymphocytes is not impaired. MSM mice carrying a p53-knockout allele were crossed with BALB/c mice heterozygous for thescidlocus and 129 offspring were obtained. They were subjected to γ-ray irradiation, 84 thymic lymphomas being generated. The tumors and host mice were genotyped ofp53andscid.Among 42 mice developing p53-deficient lymphomas,scid/+ and +/+ genotypes did not provide difference in onset and latency. Besides, allelic loss of theScidgene occurred at a high frequency in those lymphomas but the loss exhibited no allelic bias. The results suggest that thescid/+ genotype is not a modifier of loss of p53 function in the double heterozygotes.