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

Nat Genet. 1995 Mar;9(3):305-11. doi: 10.1038/ng0395-305.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division
  • Crosses, Genetic
  • DNA Primers / genetics
  • Embryo, Mammalian
  • Female
  • Fibroblasts / cytology
  • Gene Deletion
  • Genes, p53*
  • Heterozygote
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neoplasms, Experimental / genetics*
  • Neoplasms, Experimental / pathology
  • Point Mutation*
  • Polymerase Chain Reaction

Substances

  • DNA Primers