Guidelines on severity assessment and classification of genetically altered mouse and rat lines

Abstract

Genetic alterations can unpredictably compromise the wellbeing of animals. Thus, more or less harmful phenotypes might appear in the animals used in research projects even when they are not subjected to experimental treatments. The severity classification of suffering has become an important issue since the implementation of Directive 2010/63/EU on the protection of animals used for scientific purposes. Accordingly, the breeding and maintenance of genetically altered (GA) animals which are likely to develop a harmful phenotype has to be authorized. However, a determination of the degree of severity is rather challenging due to the large variety of phenotypes. Here, the Working Group of Berlin Animal Welfare Officers (WG Berlin AWO) provides field-tested guidelines on severity assessment and classification of GA rodents. With a focus on basic welfare assessment and severity classification we provide a list of symptoms that have been classified as non-harmful, mild, moderate or severe burdens. Corresponding monitoring and refinement strategies as well as specific housing requirements have been compiled and are strongly recommended to improve hitherto applied breeding procedures and conditions. The document serves as a guide to determine the degree of severity for an observed phenotype. The aim is to support scientists, animal care takers, animal welfare bodies and competent authorities with this task, and thereby make an important contribution to a European harmonization of severity assessments for the continually increasing number of GA rodents.

Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models

“…scientific-political relevance [2,9,[25][26][27]. Transparent communication about animal-based research should ideally be based on reliable and solid assessment of the burden associated with experimental models and interventions.…”

“…Due to the lack of scientific evidence, these have been largely based on expert opinion. In this context, it has also been pointed out that listing examples might imply the risk that these are applied in a rigid and unquestioning manner without consideration of study-and laboratory-specific influencing factors [27]. Moreover, the classification in categories is not sufficient, when it comes to comparative severity assessment for model comparison or validation of refinement measures.…”

Navigating Uncertainties: How to Assess Welfare and Harm in Genetically Altered Animals Responsibly—A Practical Guideline

“…Beyond this legal requirement to classify the severity, an actual severity assessment during the project ensures continuous adaptation of the protocol, and a retrospective assessment provides the opportunity to summarize findings and to gain valuable information for projects in the future. Guidance on how to assign severity can be found in Annex VIII of the directive or in several working group reports and recommendations [22][23][24][25][26][27]. Elements in an individual severity assessment include the type of technique, species, strain, stage of development, previous experience, frequency, intensity, duration of effect, and effectiveness of stress-reducing measures.…”

The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments

“…PREPARE consists not only of a 2-page checklist, but, more importantly, comprehensive webpages for each of the 15 topics on the checklist. These pages are updated regularly and provide curated links to global 3R-resources and specific guidelines, on topics such as harm-benefit assessment (e.g., [38]), severity classification (e.g., [39]), drug administration and blood sampling (e.g., [40]), and health monitoring (e.g., [41]). PREPARE also contains links to other checklists for planning specific research models, such as for stroke [42] and osteoarthritis [43].…”