Strategies for Behaviorally Phenotyping the Transgenic Mouse

Abstract

The techniques and protocols to modify the mouse genome described in this volume allow researchers to produce genetic models of a remarkable number and breadth of human disease. The generation of gene-modified mice offers profoundly powerful approaches for bringing known or purported human gene disruptions into mouse models, but the degree to which the resultant mutant mouse recapitulates the complex physiological and behavioral features of the human disease state is a key variable in the ultimate usefulness of the mouse model organism. Accordingly, the behavioral characterization of mice with novel targeted gene mutations is an important initial step in determining the potential impact of a novel mouse model. This chapter addresses strategies useful in the initial observations of the animal that assist in directing the choice of secondary tests to assess more detailed aspects of potentially disrupted behaviors that may be relevant to the disease being modeled. An initial standardized, comprehensive screen that assesses general health, reflexes, and sensorimotor functions is the first step in characterizing behavioral phenotype, and results often suggest areas where more complex complementary behavioral assays may reveal more detailed disruption of normal behavior. This sequential, standardized approach reduces variability between subjects; this chapter also addresses approaches to reducing experimental artifacts due to handling, test order, testing facility environment, and other sources. This brief overview of behavioral phenotyping approaches is intended to provide practical information to streamline initial characterization of new mouse models and maximize the usefulness of efforts to use these models to study human health and disease.