Abstract

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.

Keywords

BiologyCarcinogenesisNull alleleAlleleSuppressorGeneGene targetingMutantTumor suppressor geneMutationEmbryonic stem cellHomologous recombinationCancer researchGeneticsHomologous chromosome

MeSH Terms

AllelesAnimalsBase SequenceBlastocystBlottingSouthernDNAExonsFemaleGenesp53Genetic VectorsHeterozygoteHomozygoteMaleMiceMiceInbred C57BLMiceInbred CBAMiceTransgenicMolecular Sequence DataMutationNeoplasmsExperimentalPolymerase Chain ReactionRNAMessengerStem CellsTumor Suppressor Protein p53

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Publication Info

Year
1992
Type
article
Volume
356
Issue
6366
Pages
215-221
Citations
4656
Access
Closed

Social Impact

Social media, news, blog, policy document mentions

Citation Metrics

4656
OpenAlex
139
Influential
3612
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Cite This

Lawrence A. Donehower, Michele Harvey, Betty L. Slagle et al. (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature , 356 (6366) , 215-221. https://doi.org/10.1038/356215a0

Identifiers

DOI
10.1038/356215a0
PMID
1552940

Data Quality

Data completeness: 81%