Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
Donehower
L A
LA
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
Harvey
M
M
Slagle
B L
BL
McArthur
M J
MJ
Montgomery
C A
CA
Butel
J S
JS
Bradley
A
A
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst; D015139:Blotting, Southern; D004247:DNA / Q000737:chemistry; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA