Use of genetically manipulated animal models in MUGEN
MUGEN’s Code of Conduct is firmly focused on the application of the “3 Rs”: the long term Reduction, Replacement and Refinement of animal use in experimental protocols.
The targeted research MUGEN undertakes allows no alternative to the use of animals for the work planned, as MUGEN participants will be studying the consequences of gene mutation in different tissues and in different stages of immunological disease development. There is clearly no tissue culture alternative for such studies. Nonetheless, the focused procedures applied will undoubtedly lead to a reduction and refinement in the use of animal models in biomedical research and will diminish the “harm to benefit” ratio in the justification of animal use in the respective area of research. Additionally, network results will eventually be able to suggest cell line based assays for further research notably for drug development.
All network animal models will be registered in a central database of mutant mice available as resources for animal work to all network participants, ensuring optimal use of mice and facilities throughout the implementation of the Joint Programme of Activities (JPA). As a result, MUGEN participants shall be able to identify the available model most suitable to their research and avoid overlaps and redundancies.
Central to the Network’s activities is the consolidation and integration of existing mutant animals, which in turn would maximize their efficient use in the implementation of the JPA. Furthermore, there will be full coordination of the use by the Network of participant animal facilities and available services or of any outsourcing agreements with service providers for mouse biology resources as a means to reduce the number and costs of live animal maintenance.
Breeding and maintenance of mice is being carried out in carefully controlled and monitored conditions to ensure unnecessary stress is avoided. Welfare monitoring is an integral “code of practice” for all participants’ animal houses. In general, out of the total number of mice to be used throughout MUGEN, only a small percentage is expected to be engaged in experiments that will necessitate mild to moderate degrees of suffering. Current estimates in the Coordinator’s animal facilities, which are engaged in similar research, indicate that approximately only a 10% of the animal population used exhibits phenotypes of mild and moderate suffering. The greatest percentage of animals is free of adverse phenotypes and used in accessory functions, such as reproduction and controls or in assessing immunological phenotypes that do not necessarily involve adverse phenotypes and suffering. In cases where there is a necessity to let the animal model go through a disease development process, code of practices will apply to timely define degrees of suffering, possible interventions and endpoints. Endpoints are humane killing before development of effects is likely to exceed moderate levels of suffering.
Because of the targeted nature of the mutations that will be studied in the murine genome, in most cases it should be possible to predict potential adverse effects and to take steps to mitigate these where possible. Adverse effects due to mutations in genes with unknown function may be unpredictable. In all cases, careful welfare monitoring of the mouse colony shall apply, either by monitoring general indices such as appearance behaviour and body weight or by disease specific markers whenever specified. In case adverse effects exceed moderate levels, identified animals will be killed humanely. When in doubt, consultation with a veterinary surgeon will be sought.
MUGEN will make every effort through its web-based environment or within meetings and courses to ascertain that participant laboratories as well as the community at large is provided with:
- A framework for understanding the ethical pros and cons for the use of nonhuman animals in research and teaching.
- Information on resources and regulations regarding the care and use of transgenic animals in biomedical research.
- Theoretical underpinnings regarding the purpose and function of ethical review committees.
- Experience in thinking through issues related to biomedical engineering.