Aggression in group-housed laboratory mice: why can't we solve the problem?

Weber, Elin M.; Ahloy‐Dallaire, Jamie; Gaskill, Brianna N.; Pritchett-Corning, Kathleen R.; Garner, Joseph P.

doi:10.1038/laban.1219

Cited by 76 publications

(89 citation statements)

References 46 publications

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“…The cages were cleaned once per week, suitable nesting material was transferred to the new cage in order to reduce aggressiveness and facilitate adaptation. 21,22 Animals were weighed before moving to the clean cage.…”

Section: Ethics Statement Animals and Environmental Conditionsmentioning

confidence: 99%

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Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Åhlgren

Võikar

2019

Genes Brain and Behavior

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Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6 weeks (since 4 weeks of age) before behavioral testing. The tests addressed exploratory, anxiety‐like and stress‐related behavior (light‐dark box, open field, forced swim test, stress‐induced hyperthermia), social approach and species‐specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light‐dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well‐known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom‐line is that the environmental conditions should be described explicitly in all publications.

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Section: Ethics Statement Animals and Environmental Conditionsmentioning

confidence: 99%

“…21,22 Animals were weighed before moving to the clean cage. Room temperature was 22 ± 2 C and relative humidity 50 ± 15%.…”

mentioning

confidence: 99%

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Åhlgren

Võikar

2019

Genes Brain and Behavior

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“…When groups of mice are observed fighting excessively, or animals are found wounded, groups are generally separated and individuals can be euthanized or housed individually [7]. Not only is aggression a concern for animal welfare; pain, stress, and social isolation can also alter a number of physiological parameters, creating variability and jeopardizing scientific validity [8][9][10][11]. The issue of mouse aggression and housing is thus of high concern from both a legal, ethical, and scientific point of view and is of great importance when considering the 3Rs (to replace, reduce, and refine animal use in scientific procedures and education).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, many studies of aggression in mice use resident-intruder tests. These are staged situations that aim to trigger aggression under certain circumstances, and thus not equivalent to homecage aggression [11]. Secondly, mice in experimental studies of aggression are usually only followed during a couple of weeks while aggression in research facilities can develop over longer periods of time.…”

Section: Introductionmentioning

confidence: 99%

Group and Single Housing of Male Mice: Collected Experiences from Research Facilities in Sweden

Zidar

Weber

Ewaldsson

et al. 2019

Animals

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Simple Summary:The mouse is the most commonly used mammal in scientific research, and housed in research facilities around the world. Mice are a social species, but when housing male mice together in a confined environment in the laboratory, aggression is often observed and can be problematic. Fighting or trying to avoid fighting can be stressful. Furthermore, fighting can lead to injuries which can sometimes be fatal. Mouse aggression is therefore a significant welfare problem and has implications on the 3Rs (Replacing, Reducing, and Refining animal use in scientific procedures and education). In this study, we used a survey and workshops to collect the experiences of animal technicians, veterinarians, and researchers at Swedish research animal facilities relating to mouse aggression and what methods of preventing aggression they practice. Both group housing and single-housing as a consequence of aggression was perceived as problematic and stressful for the animals. In line with current recommendations from the literature, participants perceived that aggression occurred less if mice were grouped with litter mates at an early age, that nesting material was transferred at cage cleaning, and disturbance was kept to a minimum. Experience from practice will play a valuable part in developing guidelines for group-housed male mice.Abstract: Animals used for scientific purposes are protected by EU legislation. Social animals should be kept in stable groups that enable species-typical social behavior and provide individuals with social comfort. However, when group-housing male mice, aggression within the homecage is a common husbandry and welfare problem. Excessive fighting and injuries due to aggression can cause pain and stress, resulting in individuals being euthanized or housed individually. In addition, stress can alter physiological parameters, risking scientific validity and generating larger sample sizes. Mouse aggression, and the consequences thereof, thus opposes the 3R goals of Refining the methods to Animals 2019, 9, 1010 2 of 24 minimize potential pain and suffering and Reducing the number of animals used. Animal technicians, veterinarians, and scientists using animals have valuable information on how these problems are experienced and handled in practice. We assembled these experiences from laboratory animal facilities in Sweden, mapping problems observed and identifying strategies used to prevent mouse aggression. In line with current literature, less aggression was perceived if mice were grouped before sexual maturity, re-grouping avoided and nesting material transferred at cage cleaning. Preventing aggression will minimize pain and suffering and enable housing of stable groups, leading to more reliable scientific outcomes and is thus of high 3Rs relevance.

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“…Group housing: negative social events associated with lower lymphocyte proliferation; lower level of antigen-specific IgG; granulocytosis; lymphopenia, higher predisposition to tumor development and progression, huddling associated with amelioration of cold stress. [326][327][328][329][330] Individual housing: decreased antibody production; worsened allergic skin reaction; increased cold stress.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

Radælli

Santagostino²,

Sellers

et al. 2018

ILAR Journal

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In 1989 ILAR published a list and description of immunodeficient rodents used in research. Since then, advances in understanding of molecular mechanisms; recognition of genetic, epigenetic microbial, and other influences on immunity; and capabilities in manipulating genomes and microbiomes have increased options and opportunities for selecting mice and designing studies to answer important mechanistic and therapeutic questions. Despite numerous scientific breakthroughs that have benefitted from research in mice, there is debate about the relevance and predictive or translational value of research in mice. Reproducibility of results obtained from mice and other research models also is a well-publicized concern. This review summarizes resources to inform the selection and use of immune relevant mouse strains and stocks, aiming to improve the utility, validity, and reproducibility of research in mice. Immune sufficient genetic variations, immune relevant spontaneous mutations, immunodeficient and autoimmune phenotypes, and selected induced conditions are emphasized.

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Aggression in group-housed laboratory mice: why can't we solve the problem?

Cited by 76 publications

References 46 publications

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Group and Single Housing of Male Mice: Collected Experiences from Research Facilities in Sweden

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

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