Model Organisms in Drug Discovery

9
Chemical Mutagenesis in the
Mouse: a Powerful Tool in Drug
Target Identification and Validation
Andreas Russ, Neil Dear, Geert Mudde, Gabriele Stumm,
Johannes Grosse, Andreas Schro¨der, Reinhard Sedlmeier,
Sigrid Wattler and Michael Nehls
In the search for innovative therapeutic approaches, high-throughput in vitro
technologies such as genome sequencing, DNA microarrays and proteomics
have opened unprecedented opportunities, but they have also created new
bottlenecks in the drug discovery process because newly identified candidate
drug targets have to be linked to a physiological function in vivo. The genetic
analysis of gene function in a mammalian model organism, typically the
laboratory mouse, is one of the cornerstones in the elucidation of new
molecular pathways. In addition to the standard tools of transgenesis and
targeted mutagenesis in the mouse, chemical mutagenesis strategies have been
established recently. They can be applied to the scalable gene-driven validation
of potential targets in vivo, as well as the discovery of new therapeutic
opportunities by phenotype-driven screens for new physiological pathways.
9.1 Introduction
Starting with the discovery of recombinant DNA, and accelerating with the
genomics revolution, drug discovery strategies have undergone a transition
Model Organisms in Drug Discovery. Edited by Pamela M. Carroll and Kevin Fitzgerald
Copyright © 2003 John Wiley & Sons, Ltd. ISBN: 0-470-84893-6