Not All Mice Are Equal: Welfare Implications of Behavioural Habituation Profiles in Four 129 Mouse Substrains

Abstract

Safeguarding the welfare of animals is an important aim when defining housing and management standards in animal based, experimental research. While such standards are usually defined per animal species, it is known that considerable differences between laboratory mouse strains exist, for example with regard to their emotional traits. Following earlier experiments, in which we found that 129P3 mice show a lack of habituation of anxiety related behaviour after repeated exposure to an initially novel environment (non-adaptive profile), we here investigated four other 129 inbred mouse substrains (129S2/SvPas, 129S2/SvHsd (exp 1); 129P2 and 129X1 (exp 2)) on habituation of anxiety related behaviour. Male mice of each strain were repeatedly placed in the modified hole board test, measuring anxiety-related behaviour, exploratory and locomotor behaviour. The results reveal that all four substrains show a lack of habituation behaviour throughout the period of testing. Although not in all of the substrains a possible confounding effect of general activity can be excluded, our findings suggest that the genetic background of the 129 substrains may increase their vulnerability to cope with environmental challenges, such as exposure to novelty. This vulnerability might negatively affect the welfare of these mice under standard laboratory conditions when compared with other strains. Based on our findings we suggest to consider (sub)strain-specific guidelines and protocols, taking the (subs)train-specific adaptive capabilities into account.

Substrains of Inbred Mice Differ in Their Physical Activity as a Behavior

“…Of course, other studies clearly show that mouse substrains differ for several features other than physical activity as a behavior. For instance, it has been shown that the genetic background of the four different mouse substrains affects their vulnerability to cope with environmental challenges, such as exposure to novelty; the authors consistently suggest considering substrain-specific guidelines and protocols, taking the substrain-specific adaptive capabilities into account [31]. We totally agree with the authors of this study.…”

Experiments done in Black-6 mice: what does it mean?

“…The phenotypic differences between the genetically close sub-strains of the C57BL/6 mice, coupled with the effect of vendor highlight the possible problems associated with choosing the background for genetically modified mice, interpretation of the results and reproducibility of the findings. Obviously, these cautions are not limited only to the C57BL/6 mice [91][92][93] . Moreover, further confounds can be caused by the local breeding schemes at the research institutions 94 .…”

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

“…A wide range of behaviors can be measured, such as avoidance behavior, risk assessment, arousal, exploration, locomotor activity, habituation, social affinity and cognition 2,[8][9][10] . Additionally, the mHB can be combined with a food intake inhibition test, as well as novel object recognition test .…”