Of mice and gender: considering gender norms in rodent models

Sex and gender are often used interchangeably, though they refer to distinct concepts -the former relating to biological differences grounded in chromosomal and hormonal features and the latter to socially constructed norms, roles, and identity. In preclinical research with non-human animals, the prevailing view is that only sex differences are measurable because it is commonly accepted that rodents do not express a gender identity. However, we argue that rodents express context-specific, sex-specific behaviors which fulfill the defining requirement of gender-like norms. To explore whether sex-specific behavioral patterns in non-human animals provide evidence of gender-like norms, we focus on rodents, the most common non-human animal model. We cite examples of how their sex-specific behavior is shaped by their environment. Importantly we acknowledge that gender norms are malleable depending on the physical and social contexts - a dynamic mix of spatial environment, material composition, and social structure that jointly shapes how behavior unfolds and its meaning. Thus, our analysis examines these gender-like norms across three levels. First, we compare natural and vivarium environments to reveal the malleability of gender-like norms. We then explore how the material composition in the physical context of the vivarium cage (e.g., cage type, enrichment) can shift these norms. Finally, we show the social context within the cage (e.g., sex composition, rank, familiarity) modifies individual interactions which in turn, affects the expression of gender-like norms. Throughout we provide experimental design recommendations that advocate for the explicit consideration of both sex and gendered behavior in rodent models.

Incorporating these gender considerations will yield more effective and translatable animal models, significantly improving our ability to discover and test treatments for human toxicology, physiology, psychopathology, and neurological diseases.