Breeding and Maintenance of Immunodeficient Mouse Lines under SPF Conditions—A Call for Individualized Severity Analyses and Approval Procedures

SIMPLE SUMMARY: In the EU, the breeding of genetically modified laboratory animals is defined as an animal experiment, if the animals may experience pain, suffering or harm due to the genetic modification. In most cases, modifications of the immune system do not lead to pain, suffering, or harm given the animals are kept under specific pathogen-free housing conditions. Nevertheless, the EU working group on genetically altered animals defined SPF housing conditions as “Refinement”. According to this working group, applied refinement strategies for breeding genetically modified animals do not exclude them from project licensing. Thus, theoretical suffering, pain or harm is assumed without applying methods of actual burden assessment. Furthermore, the definition of SPF as a refinement strategy rather than a standard husbandry procedure leads to incomprehension among the scientific community in the EU. Here, we discuss the ethical basis of animal experiments as well as the current legal situation for immunodeficient animals. Furthermore, we discuss potential pain, suffering, or harm of immunodeficient animals from an immunological perspective. Finally, we briefly outline an animal welfare-oriented approach to severity assessment of immunodeficient mice. ABSTRACT: In the EU, the breeding of genetically modified laboratory animals is, by definition, an animal experiment if the offspring may experience pain, suffering, or harm. In order to determine the actual burden of genetically modified mice, established methods are available. However, the breeding of immunodeficient mice is considered an experiment requiring a permit, even if no pain, suffering or harm is observed under scientifically required defined hygienic housing conditions, as determined by established methods of severity assessment. This seems contradictory and leads to uncertainty among scientists. With this commentary, we would like to shed light on this topic from different perspectives and propose a solution in terms of individualized severity assessment and approval procedures.