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

Abstract

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.