A shared mouse-model network for disease research
An EU-funded project is integrating research resources and providing services to support access to specific mouse models for scientific investigation of the genetic foundations of human health and disease. The aim is to boost the translation of this knowledge into better treatments for patients.
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How do our genes shape our physiology, development or behaviour? One way to find out is by studying mice whose genomes can be modified to inactivate or replace specific gene functions to see how these may trigger or alleviate diseases.
The mouse is a preferred animal model for research into the genetic foundations of human health and disease. Mouse models of human disease cannot only help to identify genetic variations linked to particular types of cancer, heart disease or diabetes, but can also develop and test respective treatments.
However, producing and characterising such mouse models, known as mouse mutants, that mimick human diseases is a costly and lengthy process, and maintaining them once they have been generated involves further effort.
INFRAFRONTIER, an alliance of 29 partner organisations jointly providing what is known as a distributed research infrastructure, helps researchers to create the mouse mutant strains they need for their research and to make them available to other research groups which might also need them.
Along with access to the European Mouse Mutant Archive (EMMA), a repository that already includes 7360 mutant lines, INFRAFRONTIER provides a range of top-flight services to advance the use of mice as models of human disease.
The EU-funded project INFRAFRONTIER2020 is taking the development of this European infrastructure one step further, notably by enhancing its legal set-up and refining its operation. The project is also extending the infrastructures range of services and aligning it more closely to the needs of the medical research communities that INFRAFRONTIER was set up to serve.
We work closely with the human genetics and clinical genetics communities and support them, says project coordinator Martin Hrabĕ de Angelis, who is director of INFRAFRONTIER GmbH, Germany. INFRAFRONTIER GmbH is the coordinating non-profit entity for the infrastructure services provided for researchers.
From mouse to man
He adds: Without a detailed and proper understanding of disease biology, you will not be able to develop effective therapeutics, and you will not gain this understanding by looking just at humans. The genomes of mice are very similar to ours, and therefore mice and other model organisms are widely used as indispensable tools to interpret human genetic variation.
To support research capitalising on this resemblance, INFRAFRONTIER produces precision mouse models with specific genetic variations on demand, if the required mutant line is not already available from EMMA.
It also supports scientists with detailed analyses of the physiology and characteristics the phenotype of mutant mice. In addition, the infrastructure provides consultancy services and comprehensive training in mouse phenogenomics.
By operating a centralised, quality-controlled service that limits the need for research teams across Europe to maintain their own mouse model lines, the infrastructure is also making a substantial contribution to animal welfare, Martin Hrabĕ de Angelis adds, because the network includes all the expertise necessary to ensure animal welfare is kept at the highest standard.
Planning for the long term
INFRAFRONTIER2020 was launched in January 2017 to boost the infrastructures sustainability and help it build up new activities. Sustainability is not just a matter of funding, but also of the constant availability of the necessary specialised skills, says Michael Hagn, head of business development of INFRAFRONTIER GmbH. He adds that this particular aspect was addressed early on in the development of the infrastructure.
Thus, in INFRAFRONTIER2020, the sustainability goals include establishing a stable legal framework for the infrastructure and developing a quality management system for it. The mouse services themselves already have stringent quality procedures in place, Hagn emphasises.
The sustainability goals also involve reengineering the infrastructures database with the associated applications, as well as devising sustainable business models for INFRAFRONTIERs service platforms.
Further work to place the infrastructure on a stable footing for the future involves engaging with existing and prospective users through activities such as annual conferences and training programmes.
INFRAFRONTIER thus strives to serve the academic community with a long-term perspective, Hagn notes, adding that the fees it applies for its services are calculated to just cover the cost of these activities.
New areas of interest for INFRAFRONTIER include phenotyping services focusing specifically on ageing mice rather than only on the younger ones typically used. Many human diseases only develop later in life and therefore require ageing mice for adequate research to be done in similar mouse models, says Martin Hrabĕ de Angelis.
This new stream of activity is complemented by services such as detailed non-invasive metabolic analysis supporting research on metabolic diseases such as diabetes.
Germ-free mice are another priority, he adds. They are used to study the role of the microbiome the myriad microorganisms composing the intestinal flora in both humans and mice by colonising such mice with specific gut bacteria in a controlled fashion, adds Martin Hrabĕ de Angelis.
INFRAFRONTIER supports Europes research community by encouraging scientists to apply for free access to specific resources or services for selected research proposals involving mice models. This transnational access programme is currently implemented as part of the project.
This is the pan-European platform for models and tools to help researchers from the biomedical community to better understand the molecular underpinnings of human diseases by studying similar mouse models, says Martin Hrabĕ de Angelis.