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

## TL;DR

This paper reviews how standard housing conditions for lab mice can harm their welfare and bias research results, and suggests improvements to enhance both animal well-being and scientific quality.

## Contribution

The paper integrates ethological theory with laboratory animal welfare to argue for housing conditions as critical components of experimental design.

## Key findings

- Standard housing conditions like social isolation and poor lighting can cause chronic stress in mice.
- Improving nesting material access and thermal regulation can reduce thermal stress in mice.
- Circadian disruption from lighting regimes affects experimental outcomes and data reliability.

## Abstract

Laboratory mice are the most widely used animals in biomedical and behavioral research. Although they have been domesticated for many generations, they still retain many fundamental behavioral and physiological needs shaped by their evolutionary history. Standard laboratory housing often fails to meet these needs, which can negatively affect both animal welfare and the reliability of scientific results. This review summarizes evidence showing that common housing conditions such as social isolation, limited environmental complexity, low ambient temperature, and testing during the animals’ inactive phase can create chronic stress and alter baseline physiology and behavior in mice. These effects are often subtle but systematic, meaning they can bias experimental outcomes and contribute to poor reproducibility between studies. We highlight three key areas where welfare-related bias is particularly important: the social environment, access to nesting material and thermal regulation, and lighting regimes that disrupt circadian rhythms. Improving housing conditions in these domains is not only an ethical responsibility but also a practical strategy to enhance data quality and translational relevance. Treating housing and husbandry as integral parts of experimental design can therefore benefit both animal well-being and scientific rigor.

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.