M. Harvey et al., A MUTANT P53 TRANSGENE ACCELERATES TUMOR-DEVELOPMENT IN HETEROZYGOUS BUT NOT NULLIZYGOUS P53 DEFICIENT MICE, Nature genetics, 9(3), 1995, pp. 305-311
To test the behaviour of a mutant form of p53 in the presence and abse
nce of wild-type p53 in vivo, we mated p53-deficient mice containing a
p53 null allele to transgenic mice containing multiple copies of a mu
tant p53 gene (Val 135). Animals hemizygous for the endogenous wild-ty
pe p53 gene with the mutant transgene exhibited accelerated tumour dev
elopment and an altered tumour spectrum compared to their non-transgen
ic counterparts. In contrast, transgenic and non-transgenic animals nu
llizygous 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 f
unction activity in the absence of wild-type p53.