Related Experiment Video

Updated: Aug 14, 2026

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
17:59

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice

Published on: April 3, 2011

Involvement of p53 and p21 in cellular defects and tumorigenesis in Atm-/- mice

Y Xu1, E M Yang, J Brugarolas

  • 1Department of Biology, University of California, San Diego, La Jolla, California 92093-0322, USA. yangxu@ucsd.edu

Molecular and Cellular Biology
|June 25, 1998
PubMed

Insights

Disrupting the Atm gene in mice models ataxia-telangiectasia (A-T). The Atm gene interacts with p53, showing synergistic effects in tumorigenesis and cell cycle regulation.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Ataxia-telangiectasia (A-T) is a human genetic disorder caused by mutations in the ATM gene.
  • The mouse Atm gene disruption models A-T, exhibiting related cellular and systemic defects.
  • ATM is crucial for signaling the p53 response to DNA damage.

Purpose of the Study:

  • To investigate the synergistic roles of Atm and p53 in tumorigenesis.
  • To elucidate the role of p21 in Atm-deficient cellular proliferation defects.
  • To understand the cell cycle regulation mechanisms in Atm-mutated cells.

Main Methods:

  • Gene disruption in mice (Atm-/-, p53-/-, p21-/-).
  • Analysis of mouse embryonic fibroblasts (MEFs) for cell cycle checkpoints and proliferation.
  • Gamma-irradiation to induce DNA damage and assess cellular responses.

Main Results:

  • Atm-/- p53-/- mice exhibit accelerated lymphoma development, indicating gene synergy in tumorigenesis.
  • The G1/S cell cycle checkpoint is abolished in Atm-/- p53-/- MEFs post-irradiation.
  • Increased constitutive p21 protein levels in Atm-/- MEFs contribute to proliferative defects, which are p53-dependent and linked to enhanced p21 protein stability.

Conclusions:

  • ATM and p53 mutations synergize in tumorigenesis.
  • p53-mediated regulation of p21 stability is critical for cellular proliferation and cell cycle control in Atm-deficient cells.
  • The Atm-/- mouse model provides insights into A-T pathogenesis and potential therapeutic targets.

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