4.6 Article

p21-LacZ reporter mice reflect p53-dependent toxic insult

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 227, Issue 3, Pages 440-450

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2007.11.029

Keywords

cell cycle; drug; etoposide; hippocampus; toxicity; transgenic mice

Funding

  1. BBSRC [BBS/E/D/05251444, BBS/E/D/05251445, BBS/E/D/05251443, BBS/E/D/05251442] Funding Source: UKRI
  2. Biotechnology and Biological Sciences Research Council [BBS/E/D/05251444, BBS/E/D/05251443, BBS/E/D/05251445, BBS/E/D/05251442] Funding Source: researchfish
  3. Biotechnology and Biological Sciences Research Council [BBS/E/D/05251442, BBS/E/D/05251444, BBS/E/D/05251443, BBS/E/D/05251445] Funding Source: Medline

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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. (c) 2007 Elsevier Inc. All rights reserved.

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