Mutations in the p53 and scid genes do not cooperate in lymphomagenesis indoubly heterozygous mice

Analysis of double mutant mice of the p53 and scid genes, which have a comb ination of cell cycle checkpoint/apoptosis and DNA repair defects, shows th at the latter defect synergistically enhances lymphoma development with los s of the former function. These mice lack the ability to eliminate lymphocy tes predisposed to neoplastic transformation resulting from faulty antigen receptor gene rearrangement. Here we examine the cooperativity in double he terozygotes of p53 and scid in which normal development of lymphocytes is n ot impaired. MSM: mice carrying a p53-knockout allele were crossed with BAL B/c mice heterozygous for the scid locus and 129 offspring were obtained. T hey were subjected to gamma-ray irradiation, 84 thymic lymphomas being gene rated. The tumors and host mice were genotyped of p53 and scid. Among 42 mi ce developing p53-deficient lymphomas, scid/+ and +/+ genotypes did not pro vide difference in onset and latency. Besides, allelic loss of the Scid gen e occurred at a high frequency in those lymphomas but the loss exhibited no allelic bias. The results suggest that the scid/+ genotype is not a modifi er of loss of p53 function in the double heterozygotes. (C) 1999 Academic P ress.