We conduct ‘basic’ research to better understand how different genes function in the human body in health and disease. For example, we research which genes control the formation of our limbs and how mutations in these genes can cause limb abnormalities. We are particularly interested in understanding the biological processes that control early development of an embryo in mammals such as humans. We hope that our research will improve the lives of patients affected by genetic diseases.

What is a genetic disease?

A genetic disease is caused by a change in a person’s DNA, known as a genetic mutation, which effects how the body functions or develops. Genetic diseases can be inherited from your parents or they may be random and have no known cause.

What animals will be used in your research?

We use mice that have had their DNA altered to carry the same genetic mutations that we have found in people with different genetic diseases. The genetic mutations that we study are often found in the section of the gene that controls where in the body the gene will be expressed and at what time during development. These mutations are difficult to find and it is hard to show how they affect the person with the disease, this makes mouse models of genetic diseases important.

Why do you need to use animals? Is there no alternative?

Mice and humans share around 98 per cent of their DNA, this makes the mouse an ideal animal to study the function of different genes and apply the findings from studies using mice to humans. This type of research gives us a better understanding of the role of different genes in both health and disease.

In our research we grow cells in a culture outside of the body where possible in order to replace the need for live animals. We also use three-dimensional cell cultures called organoids that are grown in the lab from stem cells. We use these ‘mini organs’ to look at how cells and tissues are arranged in the brain, replacing some of the need for animals. However, significant findings from these laboratory based models ultimately need to be confirmed by live animal studies.

How many animals will you use?

Approximately 4000 mice that have had their DNA altered will be born per year over a period of five years as part of this research. The majority of these mice will have no invasive procedures carried out on them and are either used for breeding or are bred and humanely killed for collection of embryos or body tissues which will be analysed in detail.

How will you make sure that you use the minimum number of animals?

We work alongside staff members at the University who have considerable experience in breeding and looking after mice in the lab and who manage breeding to produce the correct number of mice needed for the experiment. This is calculated in advance using statistical tests to ensure enough animals are bred to give relevant data. A lot of the work that we do can be carried out on early stage mouse embryos before they become protected by law under the Animals in Scientific Procedures Act. At this stage the embryos are not capable of life outside of the womb and are not sentient. We can also make structures that resemble early embryos in the lab from specialised cells called embryonic stem cells. These can be used in some aspects of our research and allow us to breed fewer mice for our research.

As part of our research we freeze the embryos of mice with different genetic changes, known as mouse lines. This allows us to use the mouse line again at a later date instead of continuing to breed animals to maintain the mouse line unnecessarily. It also means that we can send these embryos to different research labs so that they do not have to create mice with the same genetic changes which would require more animals. This reduces the number of mice that will be used in research.

What is the expected harm to the animals and how will any harm be limited?

Most of the mice will be have no procedures done to them and will only be examined using non-invasive techniques before they are humanely killed using methods required by law. These mice are said to have experienced a ‘sub-threshold’ severity.

In our research, some mice will be given an injection or have a substance added to their drinking water, that changes the way their DNA behaves. We also take blood samples from some mice as part of our research. These procedures are classed as being of ‘mild’ severity.

If any mice are likely to be born with a disease that would be classed as having a ‘moderate’ severity, where possible we will study them as embryos, meaning they will not be born. Or the mice will be kept alive for the minimum amount of time and humanely killed before they develop any symptoms associated with the genetic disease.

Mice, like humans, have two copies of every gene in the body. In our research we alter one copy of a specific gene, so the mice have one altered copy and one normal copy of the gene. This means that the mice used in our research are usually healthy and show no symptoms of any disease. If mice are found to be unhealthy they will have mild symptoms of the disease that do not lead to pain or suffering. We work closely with our team of vets where we are considering creating new mouse lines or if we have any concerns.

Our mice are kept in well maintained and resourced facilities and are looked after by experienced technical staff who care about their health and well-being and use the current guidelines given by the Home Office to make sure that their welfare and health is maintained. Although the mice used in our research should show no symptoms of genetic disease they are still checked daily by technical staff for signs of ill-health or suffering.

What are the expected benefits of this research?

a.       Both short- and long-term benefits

b.      Benefits of this research specifically as well as the broader implications of the research

By studying human genetic diseases in mouse models we will improve our understanding of the biological processes that control development in the mammalian embryo. We will find out how different genes work, how the body controls different genes and what happens when this goes wrong. This will improve our understanding of how and why genetic diseases happen in humans.

We will share the results of our study with other scientists through meetings and papers published in academic journals. We will also share our findings with healthcare professionals and patient groups. All of the new mouse lines that we produce as part of this research will be shared with other scientists to help their research.

Mouse models of human genetic diseases / Animal Research by blogadmin is licensed under a Creative Commons Attribution CC BY 3.0