A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice

• Published in: Nature genetics Vol. 9; no. 3; pp. 305 - 311
• Main Authors: Harvey, Michele, Vogel, Hannes, Morris, Danna, Bradley, Allan, Bernstein, Alan, Donehower, Lawrence A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.03.1995
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Division; Classical genetics, quantitative genetics, hybrids; Crosses, Genetic; DNA Primers - genetics; Embryo, Mammalian; Female; Fibroblasts - cytology; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genes, p53; Genetics of eukaryotes. Biological and molecular evolution; Heterozygote; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Point Mutation; Polymerase Chain Reaction; Vertebrata; Heterozygozity; Protein p53; Vertebrata; Mammalia; Mouse; Rodentia; Transgenic animal; Tumor; Mutation; Carcinogenesis; Tumor suppressor gene
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0395-305

To test the behaviour of a mutant form of p53 in the presence and absence of wild-type p53 in vivo, we mated p53-deficient mice containing a p53 null allele to transgenic mice containing multiple copies of a mutant p53 gene (Val 135). Animals hemizygous for the endogenous wild-type p53 gene with the mutant transgene exhibited accelerated tumour development and an altered tumour spectrum compared to their non-transgenic counterparts. In contrast, transgenic and non-transgenic animals nullizygous for endogenous p53 developed tumours at the same rate. Thus, the mutant Val-135 p53 allele may act in vivo in a dominant negative manner in the presence of wild-type p53 but does not display gain of function activity in the absence of wild-type p53.