The Mary Lyon Centre: Advancing mouse genetics towards human disease
by Guest Author on 4 Sep 2020
It is over a century since scientists started exploring genetic diseases using mice and during that time, the laboratory mouse has become the mammal of choice for much of biological research. In 2019, UK laboratories alone used 2.5 million mice. Here, the Director of the Mary Lyon Centre and a mouse geneticist, Sara Wells, talks about the important work being done at the Centre for advancing mouse genetics towards human disease.
The biological similarities between mouse and man are obvious, we have many of the same organ systems and share the majority of our genes. However, there are some stark genetic and physiological differences between us and laboratory mice which have the potential to confound disease studies. The Mary Lyon Centre, an international resource for mouse genetics situated on the Harwell Campus, Oxfordshire, is striving to close the gap between human and mouse studies and develop improved methods for preclinical research requiring the use of genetically altered mice.
The cornerstone of much of mouse genetics research is inbred strains, these are colonies of animals produced by many generations of inbreeding. This results in large families of mice which are genetically identical. At the Mary Lyon Centre, we are using advance research tools such as CRISPR/Cas9 to introduce very precise changes into the genes of inbred strains. Genome editing (as this is sometimes referred to) involves the introduction of molecular reagents which cut and replace parts of the mouse chromosome in a very controlled and accurate way. Using these methods, we are now able to introduce the exact genetic changes seen in human patient groups.
Being able to introduce an identical disease-causing genetic change is the first step to ensuring biological and clinical relevance to human diseases. However, the human population itself is not an inbred strain, we are all genetically different. By using genome editing we can introduce a genetic change into many genetically distinct inbred strains and assess how the characteristics of those strains change, thereby starting to address aspects of genetic diversity.
Having generated a new mouse strain, how do we assess the impact of the genetic change in the mouse and compare that to human symptoms? The Mary Lyon Centre provides a platform for thorough analysis of the result of genetic changes, so called phenotyping. Many validated and quality-controlled assessments are on offer which monitor the changes in mice across many physiological systems. In addition, we are rapidly accelerating the development and implementation of devices to monitor mice in much more detail than ever before, such as the implantation of a small chip which will allow remote recording of temperature, movement and behaviour in individual mice housed in their family groups.
As a national resource, we are committed to ensuring that the mice and data we generate is available to as many researchers as possible. Our public archive of mouse strains has thousands of accessible strains and our Genome Editing Mice for Medicine Programme provides access to the molecular biology and embryology expertise at Harwell for scientists across the UK wanting to develop new mouse strains. We are very keen to forge new partnerships, providing resources and collaborations for UK biomedical scientists and will be working especially closely with anyone involved with the planned new National Mouse Genetics Network.
The Mary Lyon Centre is committed to only using animals in research when there are truly no alternatives, implementing less-invasive phenotyping assays to reduce the burden of testing and develop robust, reliable, new tests which will lead to the use of fewer animals.