A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice.
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.
Harvey
M
M
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Vogel
H
H
Morris
D
D
Bradley
A
A
Bernstein
A
A
Donehower
L A
LA
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D017353:Gene Deletion; D016158:Genes, p53; D006579:Heterozygote; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D017931:DNA Primers