Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene.
In human tumourigenesis the tumour suppressor gene most commonly affected by mutation, inactivation or allele loss is p53. Loss of p53 function is associated both with failure to maintain a normal diploid status and inability to delete cells by apoptosis following DNA damage. To investigate further the role of p53 we have generated mice carrying a large deletion within the gene. All animals homozygous for this deletion develop spontaneous tumours, predominantly lymphomas, by the age of 6 months. 10% of heterozygotes develop a range of neoplasms, with a lower predisposition towards lymphoma, by 9 months. Both tumour incidence and spectrum in heterozygotes differ from those previously reported in another p53 mutant stock, suggesting either difference in exposure to carcinogens between the two stocks, or a role for modulating genes within different genetic backgrounds. Tumours showed frequent loss of diploid status, and the majority of those arising in heterozygotes showed loss of the wild type allele. These findings are consistent with the concept that p53 acts as a tumour suppressor by preventing the propagation of DNA damage to daughter cells.
Purdie
C A
CA
CRC Laboratories, Department of Pathology, Medical School, University of Edinburgh.
Harrison
D J
DJ
Peter
A
A
Dobbie
L
L
White
S
S
Howie
S E
SE
Salter
D M
DM
Bird
C C
CC
Wyllie
A H
AH
Hooper
M L
ML
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D005434:Flow Cytometry; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D016130:Immunophenotyping; D015994:Incidence; D008223:Lymphoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D011003:Ploidies
D004273:DNA, Neoplasm