Development of a Selectively-Bred Mouse Model of Dominance and Submissiveness: Technical Considerations

Social interactions play an important role in the shaping of individual personalities and development of behavioral and physiological disturbances. Animal models represent a valuable tool in the study of the molecular and biochemical basis of social behaviors. Dominant–submissive relationship (DSR)-based models have been developed in both mice and rats for the purposes of studying the molecular basis of social behavior and psychotropic agent screening. These models have been established on the basis of the food competition paradigm. Whereas DSR models have been proven to be valid for drug testing, they have also been associated with different challenges, including low efficiency, experimental reproducibility, and testing time duration. To overcome these challenges, we employed the selective breeding approach, which has allowed us to develop mouse populations with strong characteristics of dominance and submissiveness. This model allows a dramatic increase in test efficiency, stability, and reproducibility as well as a substantial decrease in experimental duration. The selectively-bred dominant (Dom) and submissive (Sub) mice exhibit distinct differences in (a) stress-coping abilities, (b) responses to psychotropic agents, (c) inflammatory profiles, (d) gut microbiome profile, and (e) life span. Herein, we describe in detail the process of selective breeding as well as the behavioral, biochemical, and physiological characteristics of the Dom and Sub mice. We also discuss the different research directions that can be pursued by employing this model.