Despite being the most commonly used mammal in biomedical research, problems with perinatal mortality in mice have received little attention and the causes of pup death are still poorly known. Females are often housed alone with their litters and since the lost pups are generally eaten, it is commonly assumed that the mother has killed them. However, more detailed observations than have been reported previously in the literature are required to establish if the cause of death is infanticide. Litter loss can only be prevented efficiently after underlying causes have been carefully investigated and interpreted. The aim of this study was to investigate if females actively kill their pups by observing the behaviour of females and pups in litters that later were lost. We used video recordings of females that lost their entire litter to observe females in detail from parturition until the pups died. In total, 10 C57BL/6 females (wildtype and the knockouts Hfe−/− and β2m−/−) were studied, housed in Makrolon II cages with or without access to a small amount of nesting material.
Aggression among group-housed male mice is a major animal welfare concern often observed at animal facilities. Studies designed to understand the causes of male mice aggression have used different methodological approaches and have been heterogeneous, using different strains, environmental enrichments, housing conditions, group formations and durations. By conducting a systematic literature review based on 198 observed conclusions from 90 articles, we showed that the methodological approach used to study aggression was relevant for the outcome and suggested that home cage observations were better when studying home cage aggression than tests provoking aggression outside the home cage. The study further revealed that aggression is a complex problem; one solution will not be appropriate for all animal facilities and all research projects. Recommendations were provided on promising tools to minimize aggression, based on the results, which included what type of environmental enrichments could be appropriate and which strains of male mice were less likely to be aggressive.
The use of animals in research entails a range of societal and ethical issues, and there is widespread consensus that animals are to be kept safe from unnecessary suffering. Therefore, harm done to animals in the name of research has to be carefully regulated and undergo ethical review for approval. Since 2013, this has been enforced within the European Union through Directive 2010/63/EU on the protection of animals used for scientific purposes. However, critics argue that the directive and its implementation by member states do not properly consider all aspects of animal welfare, which risks causing unnecessary animal suffering and decreased public trust in the system. In this pilot study, the ethical review process in Sweden was investigated to determine whether or not the system is in fact flawed, and if so, what may be the underlying cause of this. Through in-depth analysis of 18 applications and decisions of ethical reviews, we found that there are recurring problems within the ethical review process in Sweden. Discrepancies between demands set by legislation and the structure of the application form lead to submitted information being incomplete by design. In turn, this prevents the Animal Ethics Committees from being able to fulfill their task of performing a harm–benefit analysis and ensuring Replacement, Reduction, and Refinement (the 3Rs). Results further showed that a significant number of applications failed to meet legal requirements regarding content. Similarly, no Animal Ethics Committee decision contained any account of evaluation of the 3Rs and a majority failed to include harm–benefit analysis as required by law. Hence, the welfare may be at risk, as well as the fulfilling of the legal requirement of only approving “necessary suffering”. We argue that the results show an unacceptably low level of compliance in the investigated applications with the legal requirement of performing both a harm–benefit analysis and applying the 3Rs within the decision-making process, and that by implication, public insight through transparency is not achieved in these cases. In order to improve the ethical review, the process needs to be restructured, and the legal demands put on both the applicants and the Animal Ethics Committees as such need to be made clear. We further propose a number of improvements, including a revision of the application form. We also encourage future research to further investigate and address issues unearthed by this pilot study.
Efficiency in laboratory mouse breeding is hampered by poor reproductive performance, including the loss of entire litters shortly after birth. However, the underlying mechanisms are not yet fully understood and establishing the cause of death in laboratory mouse pups can be complicated. Newborn mouse pups are generally hidden in nests, dead pups are often eaten by the female, and the widespread practice of leaving periparturient females undisturbed complicates inspection, which may delay the discovery of pup loss. In order to efficiently prevent problems with litter loss, it is important to find key factors for survival. We investigated differences in periparturient behavior between female laboratory mice whose pups survived until weaning and females whose entire litters were lost. Video recordings of 82 primiparous females of the C57BL/6 strain or knockouts with C57BL/6 background were used. The mice were observed from 24 h before until 24 h after parturition and female behaviors coded using a pre-established ethogram. The relationship between behavior and survival was analyzed using logistic models, where litter survival was regressed on the proportion of 30-s observations with at least one occurrence of the behavior. We found that females with surviving litters performed more nest building behavior during the last 24 h before parturition (p = 0.004) and spent less time outside the nest during the entire observation period (p = 0.001). Increased litter survival was also associated with more passive maternal behaviors and the female ignoring still pups less. Females that lost their litters performed more parturition-related behaviors, suggesting prolonged labor. The results indicate that maternal behavior plays a significant role in laboratory mouse pup survival. Complications at parturition also contribute to litter mortality.
Ethical evaluation of projects involving animal testing is mandatory within the EU and other countries. However, the evaluation process has been subject to criticism, e.g., that the committees are not balanced or democratic enough and that the utilitarian weighting of harm and benefit that is normally prescribed is difficult to carry out in practice. In this study, members of Swedish Animal Ethics Committees (AECs) completed a survey aiming to further investigate the decision-making process. We found that researchers and animal laypersons make significantly different ethical judgments, and hold disparate views on which ethical aspects are the most relevant. Researchers were significantly more content than laypersons with the functioning of the committees, indicating that the ethical model used suited their preferences better. We argue that in order to secure a democratic and proper ethical evaluation, the expectations of a scientific discourse must be acknowledged, while giving room for different viewpoints. Further, to fulfil the purpose of the project evaluations and meet public concern, the functions of the different AEC member categories need to be clarified. We suggest that one way of achieving a more thorough, balanced and inclusive ethical evaluation is to allow for more than one model of ethical reasoning.
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 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.