title: Mouse genetics in drug target discovery and validation: no simple answers to complex problems.
abstract: In a typical target-driven drug discovery project, the mechanism of action of the prospective therapeutic has to be validated experimentally at an early stage when pharmacological data are not yet available. This necessity has given genetic analysis of potential drug targets in model organisms a central role in the early discovery phase. The potential and the common pitfalls of mouse genetics in this context are discussed here. Using examples from recent studies in obesity and diabetes research, the role of endophenotypes, functional challenges and developmental compensation is discussed. Although unexpected results are sometimes perceived as limitations or technical problems of the mouse as a model organism, this review argues that these findings provide key information about medically relevant aspects of biology and are essential to improve oversimplistic models of pathophysiology.
authors.affiliation: University of Oxford, Genetics Unit, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK +44 1865 275248 ; +44 1865 275259 ; andreas.russ@bioch.ox.ac.uk.
authors.forename: Ap
authors.initials: A
authors.lastname: Russ
authors.forename: J
authors.initials: J
authors.lastname: Grosse