Transgenic mouse models: New tools for psychiatric research

The revolution in molecular genetics promises to identify genes that are responsible for susceptibility to psychopathology and to clarify how genes interact with environmental factors, To date, most studies reporting abnormal behavior have disrupted one specific gene and examined changes in emotionality, cognition, and consumption of food or addictive drugs. Although relating the absence of the product of a deleted gene to a specific behavior is tempting, more refined analysis has shown that the phenotype of a mutant may be a combination of a lacking gene product and the organism's attempt to compensate for the loss. Thus, an absent behavioral phenotype in a mouse with targeted gene disruption does not necessarily indicate the irrelevance of a gene product for behavior, and, vice versa, a specific behavioral abnormality in a mutant does not allow for attribution of this alteration to the lacking gene product. With these limitations in mind, it becomes clear that psychiatric research can expect major profit from the more recently developed gene technologies. The possibility of directing a mutation to specific cell types and sites in the CNS avoids the confounds imposed by changed gene function throughout the body. With few exceptions, psychiatric disorders precipitate in adulthood; thus, an animal model is preferred where ?he gene under study can be site-specifically turned on or off by a drug-driven ''genetic switch.'' Recent developments suggest that such tempting research tools will become available in the near future.