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The european mouse mutant archive infrastructure

Final Report Summary - EMMAINF (The European Mouse Mutant Archive Infrastructure)

The mouse shows great similarities in development, physiology and biochemistry to humans. This makes it a key model for research into human disease. The identification of all the genes in mice and humans in the Human Genome Project has shown that about 99 % of the genes in mice have a homologue in humans. This is important as to date around 5 000 human diseases have been shown to be caused by an error in our genetic make-up. In numerous other diseases e.g. in diabetes, errors in our genetic make-up are a contributory factor. The similarity of the mouse and human genome means that genes associated with disease in humans can be investigated in mouse models. This knowledge can then be transferred to understanding and treatment of disease in humans.

To exploit the resources emerging from initiatives such as the International Knock Out Mouse Consortium (IKMC), mouse models must be preserved and made available to the entire European biomedical research community, which is wholly dependent on new mouse models of human disease. Therefore, it is imperative that a secure, well managed central repository exists for the cryopreservation and dissemination of mouse lines which will ensure pan-European access and efficient delivery of mouse models, prerequisites for maintaining Europe's leading role in the functional annotation of the mouse genome.

EMMA - the European Mouse Mutant Archive is the primary mouse repository in Europe for the deposition and distribution of mouse disease models and research tools. The EMMA network is a non-profit making organisation and is comprised of ten partners.

A key effort of the EMMA activities was to continuously improve the operation of the EMMA network. Of central importance for the operation are the EMMA IT activities and accordingly EMMA informatics was considerably improved during the EMMAINF project by a number of means.

EMMA operations were further improved by implementing a 'grace period' to encourage submissions of valuable mouse mutants while the submitting investigator awaits publication of the first paper describing the strain. In such cases a delayed release of the strain to the public website for a period of up to two years can be granted.

With respect to EMMA's key services archiving, distribution, production of germ-free mice and dissemination of knowledge considerable progress has been made. During the EMMAINF project a total of 764.5 submissions of mouse mutants were reported for the JRA1 activity amongst which are numerous interesting disease models and valuable research tools (20 double / multiple mutants were counted with a factor of 2.5). A further 83.5 lines still in progress will be cryopreserved, leading to a total of 848 archived lines contributed by the EMMAINF program. The strong growth of the EMMA archive also leads to a continuously increasing number of requests. During EMMAINF, a total of 1,104 service requests for mouse resources were received by EMMA representing requests for 367 different mouse mutant lines from 506 different customers. Under the JRA2 activity a total of 180 lines spaces were available during the EMMAINF project to keep live mice on shelf and these were used to maintain 111 different demanded lines. For the lines kept on shelf under the JRA2 activity 632 requests were received accounting for 57 % of all requests. Due to the JRA2 funding these mice were rapidly provided to the customers. Most of the requests EMMA received during the EMMAINF project were from European researchers. In total, EMMA received 623 requests (58 % of the total number of requests) of scientists from 23 European countries. However, when single countries are taken into account the by far best EMMA customer was the US. The EMMA axenic service (JRA3) fulfilled during the EMMAINF project 20 requests for the production of germ-free mouse lines. The offered service will contribute to scientific publications of the customers. The EMMA expertise in cryopreservation techniques is disseminated by organising cryocourses. During the course of EMMAINF a total of 16 cryocourses were organised by EMMA partners of which 10 were EMMAINF funded. The courses were attended by 109 participants from 16 European countries.

A central objective of the EMMA management activities was to secure further growth of the EMMA archive by ensuring that EMMA is involved in or supporting new large scale mouse functional genomics projects such as the EUCOMM and EUMODIC projects which were launched in 2006 and 2007 respectively. Both projects aim to produce a total of up to 650 knock-out lines from the EUCOMM ES cell resource which will be archived by the EMMA network. EUMODIC aims to undertake a detailed phenotypic analysis of these knock-out lines. During the EMMAINF project for about 200 mouse mutant lines produced from the EUCOMM ES cell resource germ line transmission has been established. Archiving of these lines is ongoing. Strain related data were imported into the EMMA database in January 2009 and now EUCOMM mice can be ordered via EMMA.

The EMMAINF project made a significant contribution to the further strong increase in the overall number of submissions to the EMMA archive leading to a total of 1564 submissions by the end of the project. The publicly available archive currently consists of 1234 mouse mutant lines. A further 59 mouse mutant lines are archived but covered by a 'Grace Period' and are not yet publicly available. The most prevalent class of mutants are chemically induced mutants (483 lines). The number of transgenic lines and targeted mutant strains increased considerably to 233 lines and 366 strains with targeted mutations, respectively. Among the transgenic lines are a growing collection of currently 53 Cre-driver lines some of which comprise the most bestselling strains of the EMMA archive. The most prominent class of targeted mutants are knock-out strains of which currently 271 are distributed to EMMA customers.