Genetically altered animals in research
By altering the genetics of an animal (known as genetically altered or GA animals), the various functions of different genes can be identified more easily. In addition, GA animals can contribute to our understanding of how animals and humans develop and function, as these identified genes, or similar genes, are often also present in humans.
Most GA animals are used in genetic studies, and nearly all of them are mice and rats. They may be used in basic research to discover the function of a particular gene - for instance for studying embryonic development or the ageing of cells - or in the study of diseases.
There is a vast array of diseases and disorders which stem from the function of genes, for example cystic fibrosis, many cancers, sickle-cell anaemia, and colour blindness.
Definition of genetically altered: Where the genetic code, within some or all of the cells of an animal which determine its development and maintain its use, is changed.
Genetic alteration allows scientists to recreate human genetic diseases in a controlled experimental setting so that they can begin looking for effective treatments.
Turning on/off common genes
To understand how genes work and, in particular, how they can lead to disease, it is useful to turn them ‘on’ or ‘off’ through genetic alteration to determine their function and hopefully see how they cause disease being studied.
Genetic alteration is unethical and illegal to do in humans, so a solution is to genetically alter other animals which share common genes with humans, and use the effects to make predictions for humans. In the vast majority of cases this is done with mice as they share approximately 99% of our DNA, and are relatively easy to genetically alter, breed and house.
‘Humanised’ mice for better research into disease and treatments
A so-called 'humanised' mouse is partially achieved by adding human versions of genes, which are thought to be associated with a particular disease, into a mouse or other animal. These form ‘humanised’ animal models of the disease.
Humanised animal models also increase the ability of researchers to predict the efficiency and safety of chemicals due to their greater genetic similarity to humans.
Use of GA animals has allowed neuroscientists to decipher the function of particular genes and to create disease models. 'Knockout' models have been used in the study of Alzheimer’s disease, for example, and have been critical in understanding the neural basis of learning and memory.
This is an advancing area is the development of GA using monkeys as models of inherited neurodegenerative diseases. In 2008, researchers produced the first transgenic monkeys which expressed the Huntington’s disease gene; the animals exhibited many of the defining features of Huntington’s disease. More recent research has allowed the development of mouse models that feature these gene mutations, which are used to understand how the disease progresses and how it can be treated.
Using GA animals can help reduce the numbers of animals needed for research
Increasingly with the advance of new technology, genetic alterations offer a greater opportunity to reduce the number of animals used in biomedical research as it allows the development of generations of animals with genetic alterations which better reflect human diseases.
GA mice have also been used to replace monkeys in oral polio vaccine batch safety tests. The polio vaccine contains a small, inactive portion of the live polio and it is essential that each batch of vaccine is tested to ensure that it is safe and does not revert to the infectious virus on use. Monkeys possess virus receptors similar to those found in humans, however GA mice that express human polio receptors are now an effective replacement animal model.
Some GA animals that are bred are actually non-GA animals, why does that happen?
Current technology cannot guarantee that every required genetic alteration materialises, or occurs in the correct place and in the right cells. The practice is expensive, complicated, and time-consuming, and therefore every effort is made to get the right results. As technology improves the science of genetic alteration will improve and the surplus of animals bred but not used will decrease, for example with the new technologies such as Prime editing, and CRISPR/Cas9.
Why is the creation and breeding of GA animals sometimes classified as a severe procedure?
Procedures for the creation and breeding of GA animals involve the breeding of animals whose genes have been modified. These animals are then used to produce GA offspring for use in experimental procedures. Animals that are bred with genetic disorders, that are expected to lead to severe and persistent impairment of their general condition, are considered to have undergone a severe procedure. For further information about severity.