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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:

Replacement

• 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

Reduction

• 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

Refinement

• 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).

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