• p53;
  • mouse;
  • genetic background;
  • tumor susceptibility;
  • lymphoma


Mice with disrupted germline p53 alleles have been engineered by us and others and have been shown to have enhanced susceptibility to spontaneous tumors of various types. We monitored a large number of p53-deficient mice(p53+/− and p53−/−) and their wild-type littermates(p53+/+) of two different genetic backgrounds(129/5v and mixed C57BL/6 × 129/5v) up to 2 yr of age.p53+/− and p53−/− 129/Sv mice show accelerated tumorigenesis rates compared with their p53-deficient counterparts of mixed C57BL/6 × 129/Sv genetic background. The tumor spectra of the two strains of mice are similar except that almost half of 129/Sv p53−/− males develop malignant teratomas, whereas these tumors are rarely observed in C57BL/6 × 129/Sv mice and never in 129/Sv p53+/− males. In the study reported here, we further characterized the lymphomas that arose in the p53-nullizygous mice and found that over three-quarters of the lymphomas were of thymic origin and contained primarily immature(CD4+/CD8+) T-cells, whereas the remainder originated in the spleen and peripheral lymph nodes and were of B-cell type. The high incidence of early-onset lymphomas in the nullizygous mice makes these animals a good lymphoma model, whereas the heterozygous mice may be a useful model for Li-Fraumeni syndrome, a human inherited cancer predisposition.© 1995 Wiley-Liss, Inc