Table_1_Automated Home-Cage Monitoring During Acute Experimental Colitis in Mice.docx

For ethical and legal reasons it is necessary to assess the severity of procedures in animal experimentation. To estimate the degree of pain, suffering, distress or lasting harm, objective methods that provide gradebale parameters need to be tested and validated for various models. In this context, automated home-cage monitoring becomes more important as a contactless, objective, continuous and non-invasive method. The aim of this study was to examine a recently developed large scale automated home-cage monitoring system (Digital Ventilated Cage, DVC®) with regard to the applicability and added value for severity assessment in a frequently used acute colitis mouse model. Acute colitis was induced in female C57BL/6J mice by varying doses of DSS (1.5 and 2.5%), matched controls received water only (0%). Besides DVC® activity monitoring and nest scoring, model specific parameters like body weight, clinical colitis score, and intestinal histo-pathology were used. In a second approach, we questioned whether DVC® can be used to detect an influence of different handling methods on the behavior of mice. Therefore, we compared activity patterns of mice that underwent tunnel vs. tail handling for routine animal care procedures. In DSS treated mice, disease specific parameters confirmed induction of a graded colitis. In line with this, DVC® revealed reduced activity in these animals. Furthermore, the system displayed stress-related activity changes due to the restraining procedures necessary in DSS-treatment groups. However, no significant differences between tunnel vs. tail handling procedures were detected. For further analysis of the data, a binary classifier was applied to categorize two severity levels (burdened vs. not burdened) based on activity and body weight. In all DSS-treatment groups data points were allocated to the burdened level, in contrast to a handling group. The fraction of “burdened” animals reflected well the course of colitis development. In conclusion, automated home-cage monitoring by DVC® enabled severity assessment in a DSS-induced colitis model equally well as gold standard clinical parameters. In addition, it revealed changes in activity patterns due to routine handling procedures applied in experimental model work. This indicates that large scale home-cage monitoring can be integrated into routine severity assessment in biomedical research.

出于伦理与法律层面的考量，有必要对动物实验中操作的严重程度进行评估。为量化疼痛、痛苦、窘迫或持续性伤害的程度，需针对各类动物模型，对可提供分级参数的客观检测方法开展测试与验证工作。在此背景下，作为一种非接触、客观、持续且无创的监测手段，自动化家笼监测的重要性日益凸显。本研究旨在针对一款新近研发的大规模自动化家笼监测系统——数字通风笼（Digital Ventilated Cage，DVC®），评估其在常用急性结肠炎小鼠模型中用于严重程度评估的适用性与附加价值。本研究对雌性C57BL/6J小鼠给予不同浓度的葡聚糖硫酸钠（DSS，1.5%与2.5%）以诱导急性结肠炎，匹配对照组小鼠仅给予纯水（0% DSS）。除采用DVC®的活动监测与筑巢评分外，本研究还使用了该模型特有的检测参数，包括体重、临床结肠炎评分以及肠道组织病理学结果。在第二项研究方案中，本研究旨在探究DVC®是否可用于检测不同饲养操作方式对小鼠行为的影响。因此，本研究对比了在常规动物饲养操作中，采用隧道式抓取与尾式抓取的小鼠的活动模式差异。在经DSS处理的小鼠中，疾病特异性参数证实其诱导出了分级程度不同的结肠炎。与之相符的是，DVC®监测结果显示此类小鼠的活动量有所降低。此外，该系统还监测到，由于DSS处理组小鼠需接受必要的约束操作，其活动模式出现了与应激相关的变化。不过，隧道式抓取与尾式抓取两种操作方式间未检测到显著的活动模式差异。为开展进一步的数据分析，本研究采用二分类器，基于活动量与体重将小鼠分为两个严重程度等级：负担组与非负担组。与饲养操作对照组不同，所有DSS处理组的所有数据样本均被归类至负担组。“负担组”小鼠的占比能够较好地反映结肠炎的进展过程。综上，采用DVC®的自动化家笼监测可用于DSS诱导的结肠炎模型的严重程度评估，其效果与临床金标准参数相当。此外，该系统还可揭示实验模型研究中采用的常规饲养操作所引发的活动模式变化。这表明大规模家笼监测技术可被整合至生物医学研究的常规严重程度评估流程中。