title: Effects of genetic background on tumorigenesis in p53-deficient mice.
abstract: 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/Sv and mixed C57BL/6 x 129/Sv) 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 x 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 x 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.
authors.affiliation: Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Donehower
authors.forename: M
authors.initials: M
authors.lastname: Harvey
authors.forename: H
authors.initials: H
authors.lastname: Vogel
authors.forename: M J
authors.initials: MJ
authors.lastname: McArthur
authors.forename: C A
authors.initials: CA
authors.lastname: Montgomery
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: T
authors.initials: T
authors.lastname: Thompson
authors.forename: R J
authors.initials: RJ
authors.lastname: Ford
authors.forename: A
authors.initials: A
authors.lastname: Bradley
mesh_terms: D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D016158:Genes, p53; D005818:Genetic Engineering; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
chemical_list: D016159:Tumor Suppressor Protein p53