Trends in Pharmacological Sciences
Techniques: Reporter mice – a new way to look at drug action
Section snippets
Reporter mouse technology: from basic science to pharmacology
Reporter genes (genes that encode an easily detectable protein) transfected in eukaryotic cells have been used widely to study cis-regulatory sequences or trans-acting factors that modulate the transcriptional activity of certain promoters. The introduction of reporter genes into animal genomes provides opportunities to investigate the activity of a given promoter in the context of a living organism. Thus, the dynamics of transcription of simple or complex promoters can be quantified or, with
The ERE–Luc mouse: first example of a reporter animal for drug development
The ERE–Luc model can be considered as an interesting prototype of reporter animal for pharmacological application because it was specifically planned to study and develop ligands that are active through ER binding. Given that ERs are expressed ubiquitously in mammals, this mouse model had to report on the generalized state of activity of these receptors. The model had to be applicable to the study of the dynamics of ER activity under single or repeated stimulation. Finally, the system had to
Reporter mice as innovative tools for the generation of novel, more-selective and, hopefully, safer drugs
Reporter mice have the potential to induce a paradigm shift in future preclinical studies of pharmacologically active compounds. From the results reported in this article it appears that by using reporter mice to evaluate a novel molecule, pharmacokinetic studies can be substituted by the direct measurement of compound activity in the desired target organ; thus, the dosage of the potential drug could be established with unprecedented accuracy by the extent of its action on the target and
Concluding remarks
The major advantage of reporter animals is that they provide measurable endpoints for the evaluation of drug efficacy in all tissues of living animals. This radically changes preclinical experimentation and provides the opportunity to better understand physiological and pathological mechanisms and to evaluate and compare the effects of therapeutic treatment in healthy animals or in models of specific diseases. However, novel strategies need to be developed to overcome the present difficulties
Acknowledgements
We are grateful to European Communities (EDERA project n. QLK4CT-2002–0221; NoE EMIL and NoE CASCADE), Italian Ministry of Research and Education (COFIN n. 2002058785_001 and FIRB n. RBNE0157EH and RBNE01PASK), Telethon Foundation (GGP02336) and Italian Association for Cancer Research (AIRC) for continuous support.
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