Running in the wheel: Defining individual severity levels in mice
| Autor: | Steven R. Talbot, Svenja Biernot, Christine Häger, André Bleich, Stephanie Buchheister, Lydia M. Keubler, Manuela Buettner, Nora Weegh, Silke Glage |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Physiology Social Sciences Running Mice Severity assessment 0302 clinical medicine Phlebotomy Medicine and Health Sciences Blood and Lymphatic System Procedures Cluster Analysis Psychology Biology (General) Grading (education) media_common Mammals Animal Behavior General Neuroscience Methods and Resources Eukaryota Animal Models Colitis Body Fluids Distress Blood Experimental Organism Systems Physiological Parameters Vertebrates Female Anatomy Restraint stress General Agricultural and Biological Sciences medicine.medical_specialty QH301-705.5 Mouse Models Surgical and Invasive Medical Procedures Gastroenterology and Hepatology Motor Activity Biology Animal Welfare Research and Analysis Methods Body weight Rodents General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Model Organisms Physical medicine and rehabilitation Physical Conditioning Animal medicine Animals media_common.cataloged_instance European union Acute colitis Behavior General Immunology and Microbiology Inflammatory Bowel Disease Body Weight Organisms Biology and Life Sciences Mice Inbred C57BL Disease Models Animal 030104 developmental biology Face Amniotes Animal Studies Zoology Head Stress Psychological 030217 neurology & neurosurgery Blood sampling |
| Zdroj: | PLoS Biology, Vol 16, Iss 10, p e2006159 (2018) PLoS Biology |
| ISSN: | 1545-7885 |
| Popis: | The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly, the exact assessment of all signs of pain, suffering, and distress experienced by laboratory animals represents a prerequisite to develop refinement strategies. However, minimal and noninvasive methods for an evidence-based severity assessment are scarce. Therefore, we investigated whether voluntary wheel running (VWR) provides an observer-independent behaviour-centred approach to grade severity experienced by C57BL/6J mice undergoing various treatments. In a mouse model of chemically induced acute colitis, VWR behaviour was directly related to colitis severity, whereas clinical scoring did not sensitively reflect severity but rather indicated marginal signs of compromised welfare. Unsupervised k-means algorithm–based cluster analysis of body weight and VWR data enabled the discrimination of cluster borders and distinct levels of severity. The validity of the cluster analysis was affirmed in a mouse model of acute restraint stress. This method was also applicable to uncover and grade the impact of serial blood sampling on the animal’s welfare, underlined by increased histological scores in the colitis model. To reflect the entirety of severity in a multidimensional model, the presented approach may have to be calibrated and validated in other animal models requiring the integration of further parameters. In this experimental set up, however, the automated assessment of an emotional/motivational driven behaviour and subsequent integration of the data into a mathematical model enabled unbiased individual severity grading in laboratory mice, thereby providing an essential contribution to the 3Rs principles. Author summary Animal-based biomedical research is often accompanied by experience of discomfort or pain by the animal. Recognition of disturbed animal welfare is mandatory, and the classification and assessment of its severity is a crucial part of the legislative framework in the European Union (EU). In the present study, we analysed voluntary wheel running (VWR) behaviour as a measure of compromised welfare in a mouse colitis model. Unsupervised mathematical clustering of clinical and VWR data enabled us to allocate and classify severity levels. This cluster model was verified using VWR data from a restraint stress model and allowed us to uncover the impact of routine experimental procedures on these mice. We propose that clustering of VWR behaviour provides a useful method for assessing the severity level of experimental procedures conducted on mice. |
| Databáze: | OpenAIRE |
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