Major European mouse study reveals the role of genes in disease

Neuherberg, 31. Juli 2015. The role of over 300 genes has been revealed by DZD scientists in cooperation with colleagues across Europe in a major initiative to understand the part they play in disease and biology. The results have now been published in the journal ‘Nature Genetics’.

Since mice share 90 percent of our genes they play an important role in understanding human genetics. The European Mouse Disease Clinic (EUMODIC) brought together scientists from across Europe to investigate the functions of 320 genes in mice. Over half of these genes had no previously known role, and the remaining genes were poorly understood.

In order to study gene function, the EUMODIC consortium produced mouse lines which each had a single gene removed. These mouse lines were then analyzed in mouse clinics, where each line was assessed by a series of tests and investigations, allowing to establish the role of the missing genes. Over 80 percent of the mouse lines assessed had a characteristic that provided a clue to what the missing gene’s role might be. If the mouse fails a hearing test, for example, it suggests the missing gene has a role in hearing. In total, they carried out over 150 different tests on each mouse line.

EUMODIC was the first step towards the creation of a database of all mouse gene functions, a vision now being realized by the International Mouse Phenotyping* Consortium (IMPC). The IMPC incorporates 20 centers from across the globe with the aim over the next ten years of uncovering the role of all 20,000 genes in the mouse genome. IMPC builds on the groundwork and achievements of EUMODIC in establishing the procedures and processes to identify and catalogue the function of genes.

First author Professor Martin Hrabě de Angelis, Member of the DZD Board and Director of Institute of Experimental Genetics at the Helmholtz Zentrum München, who invented the mouse clinic concept, said: “Our findings with regard to the genes examined are now available to the scientific community as a valid data set, which can be downloaded free of charge from the IMPC (International Mouse Phenotyping Consortium) website, and form an excellent basis on which we and other research groups can develop and test new hypotheses.” This was the first time such a project has been attempted on this scale with multiple centers cooperating together from different countries. The consortium had to establish new standardized procedures to generate and assess the mouse lines and a central European database to store all the data.

All the findings from the project have been made publically available, allowing other scientists to use it in their own research. This will allow to understand more about genes we currently know very little about, and open up new avenues for research into the genetics of human disease.

Further information
* A “phenotype” is the composite of an organism’s observable characteristics. It includes not only morphological traits but also physiological properties and behavioral characteristics.

Original publication:
Hrabě de Angelis, M. et al. (2015). Deciphering mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics, Nature Genetics, DOI: 10.1038/ng.3360

Link to the Publication