Clashes with Cage Mates: When Mixing Unfamiliar Female Mice Causes Unexpected Aggression

Aggression among group-housed female laboratory mice is generally not a concern in enriched environments, and social housing is preferred to avoid potential harms associated with isolation. In this case study, however, we describe unanticipated aggression that emerged when 86 mature female mice, housed lifelong in conventional laboratory cages, were co-housed with unfamiliar weanlings. Half of the co-housing events involved moving to large, highly ‘enriched’ cages. Across all mice, aggression was only ever observed in these well-resourced conditions, and in individuals older than 35 weeks, making age and improved housing the only consistent predictors of risk. Pre-treatment behavioral profiles (including stereotypic behavior, sociability, anxiety, and anhedonia) did not reliably predict which individuals would later be aggressive. The outcomes suggest that for some older, enrichment-naïve females, the sudden availability of high-value resources may trigger potential resource guarding, and thence intense, targeted aggression toward juvenile cage mates, leading to compromised welfare in victims and necessitating early removal of the aggressor. This case raises important ethical and practical questions for refinement in laboratory rodent husbandry, such as how to enrich previously unenriched animals, whether late-life enrichment can be a welfare risk, the value and limitations of pre-mix behavioral screening, and what endpoint criteria should look like when serious welfare risks are present in only a subset of animals. Most importantly, it highlights the necessity of reporting rare but severe outcomes so that refinements arising from ‘exceptions’ can be translated into improved protocols and education across research settings. Information © The Authors 2026