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.
Highlights
Scientists studying rodents in the laboratory often attempt to account for their social needs by housing them in groups of several animals per cage[1]
We determined the stability of individual rank by calculating the frequency of individuals that maintained their social dominance rank
Because the phenotype of a mouse partly depends on its environment, scientists often make a tacit assumption that mice within the same cage are phenotypically more similar than mice housed in different cages
Summary
Scientists studying rodents in the laboratory often attempt to account for their social needs by housing them in groups of several animals per cage[1]. Research on the social dominance of laboratory mice contests this assumption, and indicates that cage-mates with different dominance ranks have different phenotypic traits[11]. This general finding implies that animals from different cages but with the same dominance rank (e.g. alpha ranked mice) have more similar phenotypic traits than cage-mates with different ranks (e.g. alpha, beta, gamma) These sub-group structures within a cage, such as social dominance, question common practices of averaging results across cage-mates or randomly selecting one animal. A recent study[33] considering both dominance rank and hierarchy, concluded that subordinate mice in highly despotic groups had significantly lower testosterone and higher levels of corticosterone than their alpha cage-mates, whereas mice living in transitive groups had similar levels of testosterone and corticosterone. All mice were tested on common paradigms in pre-clinical animal research; exploration in the open field, exploration and discrimination of a novel object, anxiety-related behavior in an elevated plus-maze, and concentration of glucocorticoid metabolites in fecal samples
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