One score to rule them all: severity assessment in laboratory mice

Abstract

18Animal welfare and the refinement of experimental procedures are fundamental aspects of 19 biomedical research. They provide the basis for robust experimental designs and reproducibility of 20 results. In many countries, the determination of welfare is a mandatory legal requirement and 21 implies the assessment of the degree of the severity that an animal experiences during an 22 experiment. However, for an effective severity assessment, an objective and exact 23 approach/system/strategy is needed. In light of these demands, we have developed the Relative 24 Severity Assessment (RELSA) score. 25 This comprehensive composite score was established on the basis of physiological and behavioral 26 data from a surgical mouse study. Body weight, the Mouse Grimace Scale score, burrowing behavior, 27 and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general 28 activity were used to investigate the quality of indicating severity during postoperative recovery. The 29 RELSA scores not only revealed individual severity levels but also allowed a comparison of severity in 30 distinct mouse models addressing colitis, sepsis, and restraint stress using a k-means clustering 31 approach with the maximum achieved RELSA scores. 32We discriminated and classified data from sepsis nonsurvivors into the highest relative severity level. 33Data from mice after intraperitoneal transmitter implantation and sepsis survivor al were located in 34 the next lower cluster, while data from mice subjected to colitis and restraint stress were placed in 35 the lowest severity cluster. Analysis of individual variables and their combinations revealed model-36and time-dependent contributions to severity levels. 37In conclusion, we propose the RELSA score as a validated tool for objective real-time applicability in 38 severity assessment and as a first step towards a unified and accessible risk assessment tool in 39 biomedical research. As an effective severity assessment system, it will fundamentally improve 40 animal welfare, as well as data quality and reproducibility. 41Laboratory Animals 3 or the European Directive on the protection of animals used for scientific 48 purposes 4 . Animal welfare describes a status of high quality of life, which relies on the consideration 49 and promotion of things to achieve good animal welfare 5,6 . Its assessment requires the monitoring of 50 animal affective states with both positive and negative valance 7 . The term severity assessment more 51 specifically addresses the categorization of negative affective states of animals under experimental 52 conditions; however, both the promotion of welfare and assessment of severity aim at the 53 recognition of any sign of suffering and thereby are essential for possible interventions to relieve the 54 burden during experiments and promote the refinement of procedures. Nevertheless, to achieve 55 compliance with scientific and regulatory requirements, an exact, evidence-based severity 56 assessment and the classification of severity ...

Comparing distress of mouse models for liver damage

“…Second, accessible tools to assess and compare distress have to be provided for the scientific community. Talbot and colleagues have started to explore such a tool, and recommend the use of a Relative Severity Assessment (RELSA) score for comparing animal models 52 . It will be important for the research community to make such tools accessible online.…”

Dopamine Transporter Knockout Rats Show Impaired Wellbeing in a Multimodal Severity Assessment Approach

“…For an ideal classification of the severity grade of the DAT KO rats, we would suggest a systematic approach as already proposed for mice ( Talbot et al, 2020 ). By applying the same wellbeing parameters in many rat models, sensitive and comparative evidence-based severity assessment will become feasible.…”

Comparative Severity Assessment of Genetic, Stress-Based, and Pharmacological Mouse Models of Depression

“…We used the RELSA ( Talbot et al, 2020 ) score to compare different models. This algorithm-based comprehensive composite score detects relative welfare impairments from multi-dimensional input parameters of physiology and behavior.…”

“…In the present study, we used established behavioral and physiological indicators for impaired welfare for a comparative analysis of models for depression in mice. Moreover, our analysis included an algorithm-based comprehensive composite score to detect welfare impairments objectively and provide a relative severity assessment (RELSA) of the different modeling strategies ( Talbot et al, 2020 ). We assessed the severity of several established models for depression based on targeted mutagenesis and stress-based treatments.…”