Animal Welfare and GEAs
A genetically engineered animal (GEA) is an animal that has had a random or targeted change in its nuclear or mitochondrial DNA (addition, deletion or substitution of some part of the animal’s genome) achieved through a deliberate human intervention.
Animal welfare concerns relate to the invasiveness of procedures used to create GEAs, the large number of animals required and the unanticipated welfare outcomes in GE offspring.
The welfare of animals used to produce the GEA strain (i.e. egg donors, surrogate mothers and stud males) may be negatively affected because invasive techniques are often used. For example, surgery is often required to implant embryos.
Many of the embryos created using GE procedures do not carry the genetic alteration of interest. This often means that large numbers of surplus animals must be created to obtain enough GEA’s with the desired alteration. In addition, invasive techniques are used (e.g. tissue samples) to determine the genotype.
The unpredictability of GEA phenotypic expression can lead to unanticipated adverse welfare outcomes. These outcomes can include:
- Disruption to physiological processes
- Poor fit between the new GEA and the environment
- Unanticipated changes to genotype or phenotype
- Pain, distress, and/or difficulties relating to the husbandry and maintenance of breeding colonies
Three Rs and GEAs
The animal welfare challenges presented by genetic engineering may be minimized by considering Three Rs approaches. For example:
- Conduct tests on the effects of GE on cell and tissue differentiation in embryonic stem cells in vitro, including using genomics and proteomics and other emerging technologies
- Create GE embryos in vitro rather than implanting them into recipient animals
- Maintain homozygous breeding pairs in order to reduce the number of animals born that do not have the desired mutation or are infertile
- Adopt strategies that maximize the use of surplus animals
- Conduct pilot studies to demonstrate that the proposed GEAs are fit for the scientific purpose
- Improve data sharing strategies to reduce duplication when creating new GEA models
- Use novel methods to create GEAs, such as "deathless transgenesis"
- Use inducible knock-out or knock-in systems so that the expression of phenotype can be controlled and only induced for a specific study period
- Use novel technology to increase accuracy and efficiency of GEA production (such as zinc finger nucleases, TALENs)
- Improve techniques for embryo transfer, such as use of non-surgical embryo transfer (NSET) techniques
- Improve techniques in the collection of tissues, determination of genotype, and individual animal identification (such as use of polymerase chain reaction techniques for genotyping)
- Maintain heterozygote breeders in situations where homozygote animals experience unacceptable morbidity, mortality or chronic disease
- Use cryopreservation to minimize potential pain and distress for animals maintained in breeding colonies, and to prevent genetic drift
This section has been adapted from the National Health and Medical Research Council (Australia) Guidelines for the generation, breeding, care and use of genetically modified and cloned animals for scientific purposes.
Welfare Assessment of GEAs
Welfare assessment of animals is intended to ensure any signs of pain and distress are detected as soon as possible, so that relevant refinement alternatives or humane endpoints can be implemented. Formal assessments of animal welfare should be part of phenotype characterization of GEAs. A GEA welfare assessment protocol will:
- reveal special needs or problems with the strain
- determine needs for handling, housing and breeding
- contribute to refinement of the model by recommending relevant humane endpoints
- prevent duplication of models already developed
It is also useful to keep centralized records of all information pertaining to a particular GEA line so that animal passports can be easily generated, and so that welfare information is effectively transferred between staff, departments and institutions.
This section has been adapted from Jegstrup et al. (2003).
For more information on GEAs, the following resources may be useful.
- Animal Welfare Committee (2007) Guidelines for the generation, breeding, care and use of genetically modified and cloned animals for scientific purposes. Canberra, Australia: Australian Government.
- This guidelines is published by the Australian government and contains a list of references on animal welfare and genetic modifications and example templates of monitoring record sheets for newly created GE animals.
- Bhogal N. and Combes R. (2006) The relevance of genetically altered mouse models of human disease. Alternatives to Laboratory Animals (ATLA) 34(4):429-454.
- Bonaparte D., Cinelli P., Douni E., Hérault Y., Maas A., Pakarinen P., Poutanen M., Lafuente M.S. and Scavizzi F. (2013) FELASA guidelines for the refinement of methods for genotyping genetically modified rodents: a report of the Federation of European Laboratory Animal Science Associations Working Group. Laboratory Animals 2013 Mar 11[Epub ahead of print].
- Dennis M. (2002) Welfare issues of genetically modified animals. ILAR Journal 43(2):100-109.
- Institute for Laboratory Animal Research (ILAR) (2006) ILAR journal: Phenotyping of genetically engineered mice 47(2).
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (2015) Genetically altered mice
- Robinson V., Morton D.B., Anderson D., Carver J. F. A., Francis R. J., Hubrecht R., Jenkins E., Mathers K. E., Raymond R., Rosewell I., Wallace J. and Wells D. J. (2003) Refinement and reduction in the production of genetically modified mice. Sixth report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement. Laboratory Animals 37 (Suppl.1):S1-S50.
- Royal Society for the Prevention of Cruelty to Animals (RSPCA) (2009) Sharing and archiving of genetically altered mice: opportunities for reduction and refinement.
- Royal Society for the Prevention of Cruelty to Animals (RSPCA) (2010) GA Passports. The key to consistent animal care.
- Wells D., Playle L., Enser B., Flecknell P., Gardiner M., Holland J., Howard B., Hubrecht R., Humphreys K., Jackson I., Lane N., Maconochie M., Mason G., Morton D., Raymond R., Robinson V., Smith J. and Watt N. (2006) Assessing the welfare of genetically altered mice. Laboratory Animals 40(2):111-114.
- Mouse Welfare Terms
- Website to aid welfare assessment of mice
- Berg A. and Bohlooly Y. (2006) The program for phenotyping of genetically modified animals at AstraZeneca. Experimental and Toxicologic Pathology 57(5-6):383-384.
- Buehr M., Hjorth J., Hansen A. and Sandoe P. (2003) Genetically modified laboratory animals – What welfare problems do they face? Journal of Applied Animals Welfare Science (JAAWS) 6(4):319-338.
- Crawley J. (1999) What’s wrong with my mouse? New York NY: Wiley-Liss.
- Jegstrup I., Thon R., Hansen A.K. and Ritske-Hoitinga M. (2003) Characterization of transgenic mice – a comparison of protocols for welfare evaluation and phenotype characterization of mice with a suggestion on a future certificate of instruction. Laboratory Animals. 37(10):1-9.
- Papaioannou V.E. and Behringer R.R. (2004) Mouse Phenotypes: A Handbook of Mutation Analysis. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press.
- Ward J.M., Mahler J., Maronpot R.R., Sundberg J.P. and Frederickson R. (eds) (2000) Pathology of Genetically Engineered Mice. Ames IO: Iowa State University Press (Blackwell Publishing).
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