Animal Research

Rodents are valuable models for the investigation of human diseases. Among the many advantages, perhaps the most important is their striking similarity to humans in anatomy, physiology, and genetics.  Over 95% of the mouse genome is similar to our own, making mouse genetic research particularly applicable to human disease. Rat represents the second model of use for disease research and will only be used here to validate the results obtained in mice in a second and different species.

The natural variation among inbred strains provides an essential system to study complex diseases involving the interaction of multiple genes, a focal point of biomedical research and drug efficacy testing. Because many of the genes responsible for complex diseases are shared between mice and humans, research in mice is crucial for the identification of genetic risk factors in the human population. Naturally occurring, spontaneous mutations also often cause afflictions in mice that mimic similar human genetic diseases. In addition, our ability to directly manipulate the mouse genome provides an incredibly powerful tool to model specific diseases for which the causative gene is known.

The rationale behind animal use in WP2 and WP3 of GO-DS21:

The mouse (and also the rat) is a favoured model for human disease research that involves the dissection of mechanisms, partly because of the availability of mouse-related tools such as antibodies, mouse models for genetic crosses, and mainly because it remains the most genetically tractable mammal for looking at interactions between complex tissue types and cell types (which are undoubtedly involved in Down Syndrome (DS) and obesity, stress or exercise (OES)). Moreover, we and other laboratories have a wealth of existing data on current models of DS and OES, including behavioral measures as well as cellular and molecular parameters, that will undoubtedly help in future analyses.

Within the GO-DS21 consortium animals as models will be used in scientific experiments. The species of choice will be the mouse and rat (and the Work Packages concerned are WP2 and WP3). The animals will be treated in respect of the Amsterdam protocol on animal welfare and protection and the following, more recent Laws:

• Directive of the European Parliament: 2010/63/EU, revising/replacing Directive 86/609/EEC, on the protection of animals used for scientific purposes adopted on 22 September 2010 and the following annexes:

1. 1. The supply of animals to authorized and competent animal facilities for use in scientific research
   2. The acquisition and validation of the competence of personnel from these establishments, whether users, breeders or providers of animals for use in scientific experimentation
   3. The agreement of the conditions of authorization, the fitting out and the operation of the establishments’ users, breeders or providers and their review
   4. The ethical evaluation and authorization of projects including the use of animals in experimental procedures

• Appendix A of the Council of Europe Convention ETS123, regarding the protection of animals used for experimental and other scientific procedures
• EU decree 2001-486 regarding the protection of vertebrate animals used for experimental or other scientific ends and following the application of the 3Rs:

1. 1. Reduce animal experimentation were possible. This will be possible by coordinating animal experimentation at the network level in order to reduce the number of experiments and by improving the flow of scientific knowledge and results between the groups
   2. Refine animal experimentation by utilizing the most appropriate practices to alleviate or minimise potential pain, suffering and distress and enhance animal well-being
   3. Replace animal experimentation, whenever possible, with alternate methodologies

All animal manipulations, which should be performed with due consideration for the economy of animal use and compassion for the suffering of the animals concerned, will only be performed by qualified personnel having sufficient experience with the described procedure protocols to minimize any possible pain and discomfort to the animals.

A humane endpoint is defined as the earliest indicator in an animal experiment of (potential) pain and/or distress that, within the context of moral justification and scientific conclusion to be met, can be used to avoid or limit the pain and/or distress by taking actions such as humane killing or terminating or alleviation of pain and distress. The humane endpoint of an animal model should be an event forming part of scientific procedure and be considered before initiation of an experiment. There should be a measure of balance with the scientific conclusion to be met: pain and distress might be intrinsic to a certain experimental model, still, the humane endpoint should neither be beyond the scientific conclusion nor the level of moral justification. With the potential for an increase in pain and/or distress, the frequency of the observations by animal welfare staff will become more numerous ranging from daily to several times each day and be recorded as scores on comparable scales.