Why did we fund this project?
This award aims to refine the lifetime experience of laboratory mice by investigating the optimal housing conditions for sexually-mature males.
Mice are the most commonly used mammalian species in animal research, 2.8 million mice were used in regulated procedures in Great Britain in 2017. Current guidelines recommend housing mice in social groups as they are highly social animals, however, aggression and fighting can occur between group-housed males leading to injuries and potentially death. The NC3Rs have led a data crowdsourcing project, which estimated the prevalence of aggression in UK facilities as approximately 15 in every 1,000 mice. Even where physical injuries are not observed, it is possible that subordinate mice may experience chronic stress as a result of aggression. Typically, aggression is managed by isolating either the aggressive or the injured mouse, but single housing is also known to be detrimental to welfare. These factors are a concern from both animal welfare and scientific perspectives, as pain/injury can alter physiological parameters and increase experimental variation.
Professor Emma Robinson and colleagues hypothesise that to improve the welfare of sexually mature male mice, the animals should be housed singly but with sensory contact with other male mice (e.g. olfactory and auditory). Emma will investigate the welfare implications of different husbandry conditions using a behavioural assay of affective state, developed with NC3Rs funding by Co-Investigator Professor Michael Mendl, as well as monitoring behavioural, physiological and biochemical measures of stress.
Mice are the most commonly used laboratory animal species. They provide researchers with a model organism of mammalian physiology which recapitulates many of the normal and pathological processes seen in human biology. One of the most important scientific advances in the last few decades has been the ability to manipulate the genetics of the mouse to create novel mutations which can be used to answer important scientific questions. Genetically altered mice now represent a large proportion of the animals being used in research and the management of mouse colonies is an area where huge benefits in animal welfare could be made but equally, if not optimal, can create significant welfare costs and cumulative suffering.
The housing environment of these animals is an area where the greatest impact over the duration of an animal's lifetime can be made. Whilst animals often do not show overt signs of distress associated with their housing environment, in male mice this is not the case. Fighting among males as they become sexually mature can lead to serious injury and even death. Even where animals do not show evidence of physical injury, there is the potential for chronic social stress within these group housed animals. Amongst the scientific community there is widespread concern about fighting in male mice and how best to manage this. Current beliefs are that mice are highly social and therefore require social housing in groups to achieve the highest standards of welfare. However, the evidence for this is quite varied and surprisingly limited. In fact, some studies in wild mice suggest that males may prefer not to live with other males. We propose that whilst mice may benefit from social interaction, this may not be offset by the social pressures which arise from group housing in a restricted (laboratory cage) environment. It is also possible that the social stress of group housing has higher welfare costs than the consequences of loss of physical contact with other mice.
A major limitation associated with previous research in this area has been a lack of objective methods to measure the impact of long term, low level social stress and cumulative suffering. In fact, it is only very recently that methods have been developed which can reliably measure behaviours which directly reflect the animals affective state and hence can provide a measure of welfare outcomes. Our research group is one of those which has pioneered methods to measure affective state in rodents. We are one of the leading groups working in the field of rodent models for depression research and we now want to apply this expertise to address our key question, 'Do male mice prefer to live on their own?' We have developed a programme of research which will look at different housing conditions and social structures. We want to provide objective evidence of the best approaches to male mouse housing and husbandry to minimise cumulative suffering and improve scientific outcomes through reduced stress and its impact on the variability of the data and therefore the numbers of animals needed for a particular experiment. Whilst our primary aim is to understand the impact of group versus individual housing, we also have designed experiments to test whether careful management of the cage environment could enable mice to achieve a more natural social structure even within the much smaller cage environment.
Our work plans provide an objective assessment of the welfare implications of different housing conditions (group vs individual, optimal enrichment) with the aim that the outcomes of this work will inform future guidance on how to best manage male mice in the laboratory environment. We will use our affective bias tasks to provide an objective and easily interpreted measure of the animal's affective state which we will complement with additional behavioural, physiological and biochemical measures of chronic stress. We will specifically test the hypothesis that sexually mature male mice prefer to live in their own territory but with access to adequate sensory information relating to conspecifics. Based on our own recent pilot research, we will also investigate the impact of temperature and whether this important, but little-studied environmental variable, has confounded previous research in this area.
We anticipate that these studies will provide clear and objective measures of the welfare implications of different housing conditions. This knowledge can be used by animal
technicians, researchers, vets, ethical review bodies, the Home Office and policy makers to make informed decisions about husbandry procedures based on knowledge of the welfare implications of the different options and the balance between providing social contact (sensory and/or physical) but avoiding social stress, fighting, injury and death.