Investigating prion disease in mouse models
Our research focuses on a group of fatal neurodegenerative brain diseases called prion diseases. A prion disease, which can also be called a transmissible spongiform encephalopathy (TSE), happens when a normal protein in the body becomes misfolded creating a prion protein. This causes progressive loss of brain tissue and body function. Prion diseases can affect both humans and animals for example, Creutzfeldt-Jakob disease (CJD) is a prion disease that affects humans and Bovine spongiform encephalopathy (BSE), also known as mad cow disease, is a prion disease that affects cattle. Prion diseases can happen spontaneously or they can be transmitted to humans from other humans or animals. Whilst prion diseases are rare, they cause a significant burden to our health service and are currently untreatable.
We conduct ‘basic’ research with the aim being to better understand how prion proteins affect the brain and how different systems in the body such as the immune system interact with the brain in prion diseases.
What animals will be used in your research?
In our research we use mice that have been bred for scientific research. Some of these mice will have had their DNA altered and are known as genetically modified mice, others will have had no changes made to their DNA.
Why do you need to use animals? Is there no alternative?
The brain is the most complex organ in the body. At the moment, we cannot accurately study the brain and how it changes in diseases such as Creutzfeldt-Jakob disease, in non-animal alternatives or in less sentient animals such as worms.
In our research we use techniques that do not require the use of animals wherever possible to reduce the number of mice we use. For example, we look at how proteins miss-fold to become prion proteins in the lab.
How many animals will you use?
We will use around 1800 mice per year over a five year period as part of this research.
How will you make sure that you use the minimum number of animals?
Our research is evaluated by a statistician who carries out statistical tests to work out the minimum number of animals needed to produce scientifically valid results. We also use tissue analysis from mice used for breeding to reduce the number of mice used as controls in our research. Control animals are mice that are not given the disease that researchers use to compare to mice that have been given the disease so that researchers can see whether the brain tissue looks different or the mice behave differently as a result of having the disease.
What procedures will the animals be involved in?
Around 80% of the mice we use in this research will undergo an inoculation procedure to inject prion containing material into brain tissue. These procedures are carried out whilst the mice are under anaesthesia by highly trained staff with care and advice from veterinary staff available at all times. This procedure is classed as being of moderate severity. After this procedure the mice will be assessed daily by experienced animal technicians for signs of clinical disease such as changes in movement or behaviour.
The remaining 20% of mice will be used for breeding purposes only before being humanely killed and having their body tissues collected for analysis. These mice are classed as having experienced sub-threshold severity.
What is the expected harm to the animals and how will any harm be limited?
As part of this research some animals will show signs of having prion disease such as weight loss or gain, changes in how the mice move around and changes in their normal behaviour. The animals may also experience some stress as part of undergoing anaesthesia. Technical staff will check the animals for ill-health every day and will report their findings to the relevant research teams and veterinary staff. The mice in our research are only allowed to show signs of the disease for two weeks before then being humanely killed. If the animals appear to be suffering before this time point they will be humanely killed.
What are the expected benefits of this research?
a. Both short and long-term benefits
b. Benefits of this research specifically as well as in the broader implications of the research
The results of our research will improve our understanding of how prion diseases affect the brain and may allow for the identification of different strains of prion proteins including the potential of these strains to be transmitted between humans or other species of animal. There is currently no cure for prion diseases, in the long term our findings may lead to treatments for prion diseases in humans and in animals.
The results we produce may impact public health policies and influence patient care through the identification of therapeutic targets and the potential production of treatments for prion diseases. In research, models of prion disease can also be used to model other neurodegenerative diseases that affect millions of people worldwide such as Alzheimer’s disease and other forms of dementia.
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