p21-LacZ reporter mice reflect p53-dependent toxic insult.
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.
Vasey
Douglas B
DB
Division of Gene Function and Development, Roslin Institute, Roslin, Midlothian, EH25 9PS, UK. douglas.vasey@bbsrc.ac.uk
Wolf
C Roland
CR
MacArtney
Thomas
T
Brown
Ken
K
Whitelaw
C Bruce A
CB
D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase