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Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice

M Harvey1, M J McArthur, C A Montgomery

  • 1Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.

Nature Genetics
|November 1, 1993
PubMed

Insights

Mice lacking the p53 gene (homozygotes) develop tumors early, while those with one p53 gene copy (heterozygotes) develop tumors later. These p53-deficient mice are susceptible to spontaneous tumors and may aid cancer research.

Area of Science:

  • Genetics and Molecular Biology
  • Oncology
  • Cancer Research

Background:

  • The tumor suppressor gene p53 plays a critical role in preventing cancer.
  • Germ-line p53 null alleles in mice lead to varying tumor susceptibility.

Purpose of the Study:

  • To investigate the tumor susceptibility and characteristics in mice with one (heterozygous) or two (homozygous) null p53 alleles.
  • To evaluate the utility of p53-deficient mice in carcinogenicity studies.

Main Methods:

  • Gene targeting to generate p53 homozygous and heterozygous mice.
  • Observation of spontaneous tumor development and types.
  • Carcinogenesis assay using dimethylnitrosamine in heterozygous mice.

Main Results:

  • Homozygous p53-deficient mice exhibited early-onset spontaneous tumors, primarily malignant lymphoma.
  • Heterozygous p53-deficient mice showed delayed onset of spontaneous tumors, predominantly osteosarcomas and soft tissue sarcomas.
  • Heterozygous mice had reduced survival following carcinogen exposure compared to wild-type controls.

Conclusions:

  • Partial p53 deficiency (heterozygosity) confers susceptibility to specific spontaneous tumors with delayed onset.
  • p53-deficient mice are valuable models for studying spontaneous and induced carcinogenesis.
  • These findings highlight the dose-dependent role of p53 in tumor suppression.

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