Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
L A Donehower1, M Harvey, B L Slagle
1Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
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.
Insights
The p53 tumor suppressor gene is crucial for preventing cancer. Mice lacking a functional p53 gene develop various tumors, highlighting its role in suppressing neoplastic disease.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Mutations in the p53 tumor suppressor gene are common in human cancers.
- The p53 gene plays a critical role in regulating cell growth and preventing tumor formation.
Purpose of the Study:
- To investigate the role of the p53 gene in mammalian development.
- To determine the necessity of p53 in preventing tumorigenesis.
Main Methods:
- A null mutation was introduced into the p53 gene using homologous recombination in murine embryonic stem cells.
- Mice homozygous for the p53 null allele were analyzed for developmental abnormalities and tumor development.
Main Results:
- Mice lacking a functional p53 gene appeared normal during embryonic development.
- These mice exhibited a high susceptibility to spontaneous development of various neoplasms by 6 months of age.
Conclusions:
- A functional p53 gene is not essential for normal embryonic development.
- The absence of p53 predisposes mammals to neoplastic diseases.
- An oncogenic mutant p53 is not required for the initiation of many tumor types.
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