Genetic approaches to modeling anxiety in animals

Anxiety disorders are a growing health problem world-wide. However, the causative factors, etiology, and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. The current status of clinical research indicates that anxiety traits and anxiety disorder in man have a genetic component, and therefore genetic modeling in animals is a logical approach to gain a greater insight into their neurobiology. However, it is also clear that the nature of these genetic contributions is highly complex. Moreover, the success of this approach is largely contingent upon the utility of available behavioral paradigms for modeling anxiety-related behaviors in mice. Animal genetic models provide a unique and comprehensive methodological tool to aid discovery into the etiology, neurobiology, and ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in man coupled with the associated multifaceted and descriptive diagnostic criteria, create challenges in both animal modeling and in clinical research. In this article, we describe some of the powerful modem genetic techniques that are uniquely amenable to the laboratory mouse and thus provide a strategy for approaching some of these challenges. Moreover, we focus on recent advances which have highlighted the relative contribution of genetic modeling in animals to the understanding of underlying neurobiology and genetic basis of anxiety disorders.