p53 Review Article

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Disrupting TP53 in mouse models of human cancers†

  1. John M. Parant,
  2. Guillermina Lozano*

Article first published online: 24 FEB 2003

DOI: 10.1002/humu.10186

Issue

Human Mutation

Human Mutation

Special Issue: Focus on p53 and Cancer

Volume 21, Issue 3, pages 321–326, March 2003

Additional Information

How to Cite

Parant, J. M. and Lozano, G. (2003), Disrupting TP53 in mouse models of human cancers. Hum. Mutat., 21: 321–326. doi: 10.1002/humu.10186

Author Information

  1. Department of Molecular Genetics, Section of Cancer Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas

*Department of Molecular Genetics, Box 11, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4095

  1. †

    For the p53 Special Issue

Publication History

  1. Issue published online: 24 FEB 2003
  2. Article first published online: 24 FEB 2003

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Keywords:

  • p53;
  • TP53;
  • cancer;
  • tumor;
  • mouse;
  • animal model;
  • MDM2;
  • MDM4;
  • suppressor;
  • oncogene

Abstract

Manipulation of the mouse genome allows emulation of the genetic defects that give rise to human cancers and evaluation of the cooperating nature of different mutations in the transformation of distinct cell types. Here we review the generation of mice with specific missense mutations in p53 (TP53) and disruption of the p53 pathway by deletion of p53 inhibitors. Missense mutations in the DNA binding domain result in viable mice with gain-of-function and dominant negative phenotypes. Loss of either of the p53 inhibitors mdm2 or mdm4 gives rise to a p53-dependent embryonic lethal phenotype. A cell can thus tolerate the absence of p53 function but not excess p53 function, a characteristic that is being exploited in the treatment of human cancers. Hum Mutat 21:321–326, 2003. © 2003 Wiley-Liss, Inc.

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