Social dominance hierarchy type and rank contribute to phenotypic variation within cages of laboratory mice

Abstract

A tacit assumption in laboratory animal research is that animals housed within the same cage or pen are phenotypically more similar than animals from different cages or pens, due to their shared housing environment. This assumption drives experimental design, randomization schemes, and statistical analysis plans, while neglecting social context. Here, we examined whether a domain of social context—social dominance—accounted for more phenotypic variation in mice than cage-identity. First, we determined that cages of mice could be categorized into one of three dominance hierarchies with varying degrees of dominance behavior between cage-mates, and low levels of agonistic behavior in the home-cage. Most groups formed dynamic hierarchies with unclear ranks, contrasting with recent accounts of stable transitive hierarchies in groups of mice. Next, we measured some phenotypic traits, and found that social dominance (i.e. dominance hierarchy type and degree of dominance behavior) consistently accounted for some phenotypic variation in all outcome measures, while cage-identity accounted for phenotypic variation in some measures but virtually no variation in others. These findings highlight the importance of considering biologically relevant factors, such as social dominance, in experimental designs and statistical plans.

Sexually divergent effects of social dominance on chronic stress outcomes in mice

“…A cumulative DS for the four baseline days of the SB assessment was used as a final measure of social dominance. In line with previous studies (18)(19)(20)(21)(22), we were able to detect a stable hierarchical structure in both sexes (Figure 1a).…”

“…These types of relationships have classically been studied in male animals, as female mice have usually appeared more communal and displayed limited aggression (17). Recent work, however, has demonstrated that female laboratory mice also form hierarchies that appear quite similar to those seen in males, accompanied by some of the same dominance-related physiological markers, such as differences in corticosterone levels (18)(19)(20)(21)(22). Thus, we examined social dominance status as a putative mediator of sex differences in the response to adverse events.…”

What it takes to be at the top: The interrelationship between chronic social stress and social dominance

“…Thus, there is a need to expand our knowledge of stress-related factors influencing social behaviours for the purposes of developing appropriate therapeutics. Refinement of animal models that currently assumes that shared housing implies greater phenotypic similarity though recent studies showing social dominance accounted for more variation in mice than cage-identity [47] would be useful to systematically study the behavioural and physiological consequence of social stress. correlates with rankings from three other dominance tests: urine marking assay, UMA (p=0.0509); agonistic behaviour test, ABT (p=0.0229); and the warm spot test, WST (p=0.0090).…”

Social dominance mediates behavioral adaptation to chronic stress in a sex-specific manner

“…Wild and laboratory rodents form complex and dynamic social structures which typically involve the formation of dominance hierarchies (Kondrakiewicz et al, 2019). These have been observed in the lab in group sizes ranging from three to over a dozen individuals (Horii et al, 2017;Varholick et al, 2019;Wang et al, 2014). Hierarchies improve social stability and reduce severe conflicts and aggression (Curley, 2016).…”

“…These types of relationships have classically been studied in male animals, as female mice have usually appeared more communal and displayed limited aggression ( König and Lindholm, 2012 ). Recent work, however, has demonstrated that female laboratory mice also form hierarchies that appear quite similar to those seen in males, accompanied by some of the same dominance-related physiological markers, such as differences in corticosterone levels ( Schuhr, 1987 ; van den Berg et al, 2015 ; Varholick et al, 2019 ; Varholick et al, 2018 ; Williamson et al, 2019 ). Thus, we examined social dominance status as a putative mediator of sex differences in the response to adverse events.…”