p21-LacZ reporter mice reflect p53-dependent toxic insult

Douglas B. Vasey, C. Roland Wolf, Thomas MacArtney, Ken Brown, C. Bruce A. Whitelaw

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    9 Citations (Scopus)

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

    Original languageEnglish
    Pages (from-to)440-450
    Number of pages11
    JournalToxicology and Applied Pharmacology
    Volume227
    Issue number3
    DOIs
    Publication statusPublished - 15 Mar 2008

    Keywords

    • cell cycle
    • drug
    • etoposide
    • hippocampus
    • toxicity
    • transgenic mice
    • KINASE INHIBITOR GENE
    • CELL-CYCLE ARREST
    • TRANSGENIC MICE
    • P53-INDEPENDENT PATHWAY
    • INDEPENDENT EXPRESSION
    • P21(WAF1) EXPRESSION
    • TUMOR-SUPPRESSOR
    • P21 WAF1/CIP1
    • DNA-DAMAGE
    • DIFFERENTIATION

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