Ethological Constraints and Welfare-Related Bias in Laboratory Mice: Implications of Housing, Lighting, and Social Environment.

Laboratory mice are the most widely used model organisms in biomedical and behavioral research, yet growing concerns regarding reproducibility and translational validity have highlighted the substantial influence of housing and husbandry conditions on experimental outcomes. Although domestication is often assumed to have rendered laboratory mice fully adapted to artificial environments, evidence from ethology indicates that many core behavioral and physiological needs remain conserved. As a result, standard laboratory housing may generate chronic stress, alter behavior, and introduce systematic bias into experimental data. This narrative review critically examines how ethological constraints persisting after domestication interact with key environmental factors, social housing, environmental enrichment, ambient temperature, and lighting regimes to shape welfare and experimental validity in laboratory mice. Rather than providing an exhaustive overview of mouse behavior, the review adopts a problem-oriented and solution-focused approach, highlighting specific welfare-related mechanisms that can distort behavioral and physiological readouts. Particular attention is given to social isolation and aggression in male mice, the role of nesting material in mitigating thermal stress, and the effects of circadian disruption under standard and reversed light-dark cycles. By integrating ethological theory with laboratory animal welfare research, this review argues that housing conditions should be regarded as integral components of experimental design rather than secondary technical variables. Addressing welfare-related bias through evidence-based refinement strategies is essential for improving reproducibility, enhancing data interpretability, and strengthening the scientific validity of mouse-based research.