If only they could talk - genetic mouse models for psychiatric disorders

The advent of advanced molecular genetics methods has revolutionized biology, both in terms of identifying gene candidates and, once identified, in terms of manipulating gene function in the experimental setting to address issues of causality and mechanism. Mice are currently the most genetically tractable animal model available and have contributed significantly to furthering our understanding of gene action across multiple areas of biology and medicine. However, using mice to model psychiatric conditions raises particular challenges because of the complex and perhaps unique phenotypes affected by disorders such as autism, schizophrenia, attention deficit hyperactivity disorder, depression, and personality disorder. In this chapter, we present a realistic view of what can be modeled in this area. We discuss the concept of endophenotypes (intermediate traits), and how endophenotypes can be used to address the complexity of the clinical conditions. We also discuss the practicalities of carrying out valid behavioral studies in mice, taking in the issues raised by the ethobiological vs artificial approach debate and emphasize the positive contribution made by the increasing use of operant behavioral paradigms in mice. We conclude that, although we are very much at the “work in progress” stage, it is likely that mouse models will be of major importance in ensuring that psychiatry gets its share of the genomic dividend