p21-LacZ reporter mice reflect p53-dependent toxic insult

Toxicol Appl Pharmacol. 2008 Mar 15;227(3):440-50. doi: 10.1016/j.taap.2007.11.029. Epub 2007 Dec 14.

Abstract

There is an urgent need to discover less toxic and more selective drugs to treat disease. The use of transgenic mice that report on toxic insult-induced transcription can provide a valuable tool in this regard. To exemplify this strategy, we have generated transgenic mice carrying a p21-LacZ transgene. Transgene activity reflected endogenous p21 gene activation in various tissues, displayed compound-specific spatial expression signatures in the brain and immune tissues and enabled p53-dependent and p53-independent responses to be identified. We discuss the application of these mice in delineating the molecular events in normal cellular growth and disease and for the evaluation of drug toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions*
  • Gene Expression / drug effects
  • Genes, Reporter
  • Mice
  • Mice, Transgenic*
  • RNA, Messenger / analysis
  • Tissue Distribution
  • Transgenes
  • Tumor Suppressor Protein p53 / genetics*
  • beta-Galactosidase / analysis
  • beta-Galactosidase / genetics*

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • beta-Galactosidase