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Refinement strategies in breeding and keeping of laboratory mice play a pivotal role in assuring the best possible solution as long as animal based research is indispensable. Furthermore, Refinement is one of the three Rs proclaimed by Russel and Burch in 1959 that found their way into the current European legislative on the protection of animals used for scientific purposes.
In Germany a majority of 72,83 percent of all vertebrates used in experiments are mice, totaling over two million individuals. Almost all used laboratory mice are descendants of the house mouse (Mus musculus). The domestication of mice started at the beginning of the 17th century, when mice were kept and bred for different intentions and led to its proceeding domestication. In Great Britain mice were already in the focus as objects of study, but they were as well popular within amateur breeders that created the so-called “fancy mice”. Subsequent and more and more professional breeding led to the emerging of the first inbred mouse strains in 1909. This launched a cascade that enables researchers today to draw on a reservoir of over 450 inbred strains of mice. The necessity of mouse models becomes visible when keeping in mind that almost 90% of the 106 Nobel Prizes awarded for Physiology or Medicine included research relying on them. To understand the basic needs of laboratory mice it is essential to have a closer look at their ancestors. They are still living among us as wild mice with either a feral, non-commensal way of life or they live as commensals associated with humans. The domestication did not change much in the behavior of mice as they still are nocturnal animals with a strong basic need for living in a group. But some of the basic changes coming along with domestication are applicable for laboratory mice as well, as they are usually less aggressive and more easily to tame than their wild relatives.
The experimental aspect of the thesis consists of two parts that both contribute to gain knowledge about minimizing the lifelong experience of pain, suffering, distress or long-lasting harm for laboratory mice. The first part aims to refine the breeding methods and the second part is a new approach to create a mouse-human relationship as well as to add a new form of enrichment - cognitive enrichment.
The evaluation of different breeding conditions is consistent with data found in literature that in not profitable conditions postnatal litter loss reaches numbers up to 50 percent. In detail, the present study evaluated the impact of an impoverished, a super-enriched and a standard-enriched condition from the prenatal period until weaning of the offspring. A solid and constant breeding success was discovered in the standard enriched cage. The superenriched condition did provide more unpalatable results concerning litter loss and pup growth. The most prominent finding was the detrimental high litter losses and the delayed pup development in the impoverished condition. The result that the highest prevalence of pup mortality occurred during the first four days after birth, leads to the conclusion, that if the usually counting of pups at weaning is going on, a huge amount of infant death is not recorded. To get a hint of how much influence the prenatal condition has on the maternal quality and thus on the offspring’s development, we tested a group with a change of the condition from impoverished and super-enriched to standard enrichment on P1. The swapping did not result in a prevention of perinatal litter loss. But one can estimate, that there was a certain effect of the variation in enrichment as the neonatal weight gap between the groups was closed until weaning. But not just a tribute to Refinement is approached but due to a better knowledge of the prevention of litter loss, a reduction of the animal number can be realized.
We successfully overcame the challenge to create a positively connoted mouse-human relationship and to introduce a PRT into the keeping of laboratory mice. Previous research provided the information that gentle handling protocols contribute to more relaxed mice. Enrichment is one major factor enabling mice to interact with their surroundings, and by manipulating things, they gain control over their environment. Control and the possibility to predict what is likely to happen next have a deep impact on the stress level. This study concentrated on clicker-training with one intention of an escalated handling protocol and with another intention of providing a new form of enrichment- cognitive enrichment. In clickertraining positive reinforcement consists of a chain of two reinforcers. The primary reinforcer is the food reward and a second reinforcer- a click is added to build up a time bridge between the strengthened behavior and an upcoming reward. Our little fellow creatures differ in their personality, even though they have an equal genetic background and born and raised under the same conditions. The food reward must address the motivation of each mouse, because motivation is the underlying reason why mice are participating in training. Further the cognitive abilities of mice turned out to be more than enough to perform the assigned tasks. The clicker-training of mice turned out to be quite simple. The evaluation of different behavioral experiments stress that trained mice are more confident in the interaction with humans and show less stress related and less depression like behaviors. In addition, stress reduction leads to a lower variability among experimental mice which results in a reduction of the amount of needed subjects and leads to data with a higher quality. This study proposes that clicker-training improves Refinement as well as reduction and thereby contributes in the implementation of the 3R-principle of Russel and Burch.