The epidemiology of fighting in group-housed laboratory mice

Abstract

Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most common potentially preventable morbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression induced by introducing a stimulus mouse into the home-cage of a singly housed mouse (i.e. the resident/intruder test). However, fighting occurring in mice living together in long-term groups under standard laboratory housing conditions has barely been studied. We performed a point-prevalence epidemiological survey of fighting at a research institution with an approximate 60,000 cage census. A subset of cages was sampled over the course of a year and factors potentially influencing home-cage fighting were recorded. Fighting was almost exclusively seen in group-housed male mice. Approximately 14% of group-housed male cages were observed with fighting animals in brief behavioral observations, but only 14% of those cages with fighting had skin injuries observable from cage-side. Thus simple cage-side checks may be missing the majority of fighting mice. Housing system (the combination of cage ventilation and bedding type), genetic background, time of year, cage location on the rack, and rack orientation in the room were significant risk factors predicting fighting. Of these predictors, only bedding type is easily manipulated to mitigate fighting. Cage ventilation and rack orientation often cannot be changed in modern vivaria, as they are baked in by cookie-cutter architectural approaches to facility design. This study emphasizes the need to invest in assessing the welfare costs of new housing and husbandry systems before implementing them.

Exploring Refinement Strategies for Single Housing of Male C57BL/6JRj Mice: Effect of Cage Divider on Stress-Related Behavior and Hypothalamic-Pituitary-Adrenal-Axis Activity

“…Order effects of testing have been shown to affect the stress response in female mice that were socially housed (Arndt et al, 2009). Although this effect was not apparent in males (Arndt et al, 2009), we alternated the within-cage testing order of mice to avoid possible effects on endocrinological parameters (Theil et al, 2020).…”

“…Our study has a few limitations. First of all, we used male mice as the prevalence of aggression in group housed mice, which is often used a reason to single house mice, is almost completely restricted to male mice (Theil et al, 2020). However, the effects of single housing in female mice should also be considered when single housing is required for experimental purposes, given female mice are more socially active than males (Palanza et al, 2001;An et al, 2011;Palanza and Parmigiani, 2017;Arakawa, 2018).…”

Strain and sex differences in somatosensation and sociability during experimental autoimmune encephalomyelitis

“…We interpreted this as the mice being eager to socialize despite their neurologic deficits. We were surprised about this finding at first, because male SJL mice are well known to exhibit extreme levels of aggression ( Azkona and Caballero, 2019 ; Theil et al., 2020 ; Van Loo et al., 2003 ). Indeed, male SJL mice aggression even among littermates is so severe that it is consider inhumane not to house individuals separately ( Azkona and Caballero, 2019 ; Theil et al., 2020 ; Van Loo et al., 2003 ).…”

“…We were surprised about this finding at first, because male SJL mice are well known to exhibit extreme levels of aggression ( Azkona and Caballero, 2019 ; Theil et al., 2020 ; Van Loo et al., 2003 ). Indeed, male SJL mice aggression even among littermates is so severe that it is consider inhumane not to house individuals separately ( Azkona and Caballero, 2019 ; Theil et al., 2020 ; Van Loo et al., 2003 ). We were expecting male SJL mice to dislike the presence of a novel mouse to the extent of showing signs of aggression when entering the mouse occupied chamber or by avoiding that chamber entirely.…”

Does vendor breeding colony influence sign- and goal-tracking in Pavlovian conditioned approach? A preregistered empirical replication

“…For example, betweenexperimenter effects have been reported in rodents, such as olfactory analgesia associated with human male experimenters [63]. There are also some reports of seasonal or circannual effects in rats and mice, but these effects are not always large or consistent [64,65]. The present study controlled for these potential confounds by direct empirical testing of within-vendor breeding colony effects, holding experimenter and time of year constant across experimental groups.…”