Abstract
Severity assessment in laboratory animals is an important issue regarding the implementation of the 3R concept into biomedical research and pivotal in current EU regulations. In mouse models of inflammatory bowel disease severity assessment is usually undertaken by clinical scoring, especially by monitoring reduction of body weight. This requires daily observance and handling of each mouse, which is time consuming, stressful for the animal and necessitates an experienced observer. The time to integrate to nest test (TINT) is an easily applicable test detecting disturbed welfare by measuring the time interval mice need to integrate nesting material to an existing nest. Here, TINT was utilized to assess severity in a mouse DSS-colitis model. TINT results depended on the group size of mice maintained per cage with most consistent time intervals measured when co-housing 4 to 5 mice. Colitis was induced with 1% or 1.5% DSS in group-housed WT and Cd14-deficient mice. Higher clinical scores and loss of body weight were detected in 1.5% compared to 1% DSS treated mice. TINT time intervals showed no dose dependent differences. However, increased clinical scores, body weight reductions, and increased TINT time intervals were detected in Cd14 -/- compared to WT mice revealing mouse strain related differences. Therefore, TINT is an easily applicable method for severity assessment in a mouse colitis model detecting CD14 related differences, but not dose dependent differences. As TINT revealed most consistent results in group-housed mice, we recommend utilization as an additional method substituting clinical monitoring of the individual mouse.
Highlights
An important change regarding the legislation for the protection of laboratory animals has been the implementation of an exact severity assessment of all procedures undertaken on laboratory animals in the Directive 2010/63/EU on the protection of animals used for scientific purposes
TINT time intervals were elevated in Cd14-/- mice treated with 1% dextran sulphate sodium (DSS) beginning from day 5 post colitis-induction and increased slightly until the end of the experiments (Fig 4B)
In 1.5% DSS treated Cd14-/- mice elevated TINT time intervals were observed beginning from day 5 post colitis-induction sustaining on the same level until the end of the experiments (Fig 4C). 1.5% DSS treated wild type (WT) mice responded with slightly increased TINT time intervals on day 5 post colitis-induction
Summary
An important change regarding the legislation for the protection of laboratory animals has been the implementation of an exact severity assessment of all procedures undertaken on laboratory animals in the Directive 2010/63/EU on the protection of animals used for scientific purposes. To investigate the complex interaction of genetic and microbial factors and determine the exact components leading to the development of inflammation, animal models of IBD have been widely used [5, 6] These experimental colitis models can be categorized with regard to the respective cause of inflammation into chemically induced models, spontaneously occurring models, genetically engineered models and cell/adoptive transfer models [7]. We aimed to evaluate whether the time-to-integrate-to-nest test (TINT) is suitable to detect disturbed animal welfare during the development of intestinal inflammation and whether it provides benefits over or in addition to a standard clinical scoring system This performed test is based on the investigation of the strongly motivated nesting behavior of mice and detects disturbed animal welfare in consequence of painful surgical procedures [12, 13]. Comparing two different mouse strains (WT vs Cd14-/-) treated with two different DSS doses (1% vs 1.5%) we analyzed whether the employed severity assessment strategy was sensitive enough to detect strain or DSS dose specific differences
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