The European Mouse Mutant Archive – EMMA
The European Mouse Mutant Archive – EMMA is a non-profit repository for the collection, archiving (via cryopreservation) and distribution of relevant mutant mouse strains essential for basic biomedical research. The laboratory mouse is the most important mammalian model for studying genetic and multi-factorial diseases in man. The comprehensive physical and data resources of EMMA support basic biomedical and preclinical research, and the available research tools and mouse models of human disease offer the opportunity to develop a better understanding of molecular disease mechanisms and may provide the foundation for the development of diagnostic, prognostic and therapeutic strategies.
EMMA is supported by the partner institutions, national research programs and by the EC's Research and Innovation programme Horizon 2020 (H2020-EU.184.108.40.206. Developing new world class research infrastructures).
EMMA is a founding member of the Federation of International Mouse Resources (FIMRe)
EMMA's primary objective is to establish and manage a unified repository for maintaining medically relevant mouse mutants and making them available to the scientific community. Therefore, EMMA archives mutant strains and distributes them to requesting researchers. EMMA also hosts courses in cryopreservation to promote the use and dissemination of frozen embryos and spermatozoa. Dissemination of knowledge is further fostered by a dedicated resource database.
The EMMA network is a partnership of several laboratories and other institutions throughout Europe. The current membership includes the CNR Campus "A. Buzzati-Traverso" in Monterotondo, Italy (core structure), the CNRS Centre de Distribution, de Typage et d'Archivage animal in Orleans, France, the MRC Mammalian Genetics Unit in Harwell, UK, the Karolinska Institutet in Stockholm, Sweden, the Instituto Gulbenkian de Ciência in Oeiras, Portugal, the Helmholtz Zentrum München, Institute of Experimental Genetics in Munich, Germany, the EMBL European Bioinformatics Institute in Hinxton, UK, the GIE-CERBM Institut Clinique de la Souris, Illkirch, France, the Wellcome Trust Sanger Institute in Hinxton, UK, the CSIC Centro Nacional de Biotecnología in Madrid, Spain, the BSRC "Alexander Fleming" in Vari, Greece , the Institute of Molecular Genetics in Prague, Czech Republic, the Biocenter Oulu, Finland, the University of Veterinary Medicine in Vienna, Austria, the Netherlands Cancer Institute and the Tel Aviv University in Israel. The EMMA network is directed by Professor Martin Hrabé de Angelis who heads the Institute of Experimental Genetics at the Helmholtz Zentrum München. To ensure the operation of such a large and international enterprise an effective management structure consisting of several components was implemented. EMMA is open for the incorporation of new members into the current network and detailed guidelines for this process are established.
Prof. Martin Hrabé de Angelis was elected as EMMA Director by the EMMA Board of Participating Directors. He is also director of the Institute of Experimental Genetics and of the German Mouse Clinic (GMC) at the Helmholtz Zentrum München. Prof. Hrabé de Angelis is responsible for the overall coordination of EMMA. As EMMA Director, he leads the Board of Participating Directors, supervises the Project Office and reports to the Advisory Board.
The EMMA Project Office is based at the Helmholtz Zentrum München (HMGU) at the Institute of Experimental Genetics of Prof. Martin Hrabé de Angelis. The Project Office is run by two project managers, namely Dr. Michael Raess M.Sc. and Dr. Sabine Fessele PMP.
This board consists of the directors of each of the EMMA partner institutions. It is headed by the EMMA Director and discusses, agrees and decides on the recommendations from the Advisory Board and the Technical Working Group. Members of the Board of Participating Directors are:
- BSRC Alexander Fleming, Vari / Athens, Greece: George Kollias
- CERBM-GIE, ICS, Illkirch / Strasbourg, France: Yann Herault
- CNR / Monterotondo, Italy: Alessandro Soluri
- CNRS / CDTA, Orléans: France: Cécile Fremond
- CNB/CSIC, Madrid, Spain: Lluis Montoliu
- EMBL/EBI, Hinxton, UK: Helen Parkinson
- Helmholtz Zentrum München, Munich, Germany: Martin Hrabé de Angelis
- Instituto Gulbenkian de Ciencia, Oeiras, Portugal: Jocelyne Demengeot
- Institute of Molecular Genetics ASCR, Prague, Czech Republic: Radislav Sedlacek
- Karolinska Institute, Stockholm, Sweden: Brun Ulfhake
- MRC Mammalian Genetics Unit, Harwell, UK: Steve Brown
- Netherlands Cancer Institute, Amsterdam, The Netherlands: Jos Jonkers
- Sanger Institute, Hinxton, UK: Ramiro Ramirez-Solis
- Tel Aviv University, Tel Aviv, Israel: Fuad Iraqi
- University of Oulu, Oulu, Finland: Reetta Hinttala
- University of Veterinary Medicine, Vienna, Austria: Thomas Rülicke
This panel is composed of leading hands-on scientists or technicians from every partner. It develops and agrees on EMMA Standard Operation Protocols (SOPs) for quality control, archiving and distribution. The group's members also build a platform to discuss scientific and technical problems and upcoming trends in the field of strain archiving, animal husbandry and distribution of living animals and frozen germplasm. Members of the group are:
- BSRC Alexander Fleming, Vari / Athens, Greece: Dimitris Kontoyiannis, Kostas Bozonelos
- CERBM-GIE, ICS, Illkirch / Strasbourg, France: Abdel Ayadi, Mohammed Selloum, Phillippe Andre
- CNR / Monterotondo, Italy: Raffaele Matteoni, Marcello Raspa, Ferdinando Scavizzi, Marzia Massimi
- CNRS / CDTA, Orléans, France: Cécile Fremond, Karine Maillard, Karine Jambou
- CNB/CSIC, Madrid, Spain: Julia Fernandez, María Jesús del Hierro
- EMBL/EBI, Hinxton, UK: Alba Gomez
- Helmholtz Zentrum München, Munich, Germany: Susan Marschall, Daniela Mayr
- Instituto Gulbenkian de Ciencia, Oeiras, Portugal: Joana Bom, Manuel Rebelo
- Institute of Molecular Genetics ASCR, Prague, Czech Republic: Jana Kopkanova, Sandra Potysova
- Karolinska Institute, Stockholm, Sweden: Johannes Wilbertz, Zuzana Khoshidi
- MRC Mammalian Genetics Unit, Harwell, UK: Martin Fray, Rachel Summerfield
- Netherlands Cancer Institute, Amsterdam, The Netherlands: Paul Krimpenfort
- Sanger Institute, Hinxton, UK: Catherine Ingle
- University of Oulu, Oulu, Finland: Reetta Vuolteenaho, Anne Heikkinen, Reetta Hinttala
- University of Veterinary Medicine, Vienna, Austria: Auke Boersma
- INFRAFRONTIER GmbH, Sabine Fessele, Fei Song, Manoj Kumar Chinnasamy, Philipp Gormanns, Montse Gustems
The Advisory Board consists of experts in the field of modern mammalian genetics and supervises the EMMA network. This committee reviews and discusses the priorities set up by the EMMA Board of Participating Directors and gives advice. It also has responsibility for ensuring that the repository is run at high standards. Input from the scientific community is ensured by the inclusion of a user representative in the AVB. To support EMMA's commitment to establishing the highest possible animal welfare standards the AVB also includes an expert in animal welfare and ethics. Members of the AVB are:
- Ian Jackson, MRC Human Genetics Unit, Edinburgh, UK
- Maja Bucan, University of Pennsylvania School of Medicine, Philadelphia, USA
- Janan Eppig, The Jackson Laboratory, USA
- Jan-Bas Prins, University of Leiden, Medical Centre, The Netherlands
The external Evaluation Committee consists of experts from the field of modern mouse genetics and ensures access to valuable mouse mutant strains. In cooperation with the Project Office, a major activity is the setting of priorities with regard to which strains of mice will be deposited in the repository. New members are proposed by the Advisory Board and appointed by the Board of Participating Directors. Members of the Evaluation Committee are:
- Johannes Beckers, Helmholtz Zentrum München - German Research Centre for Environmental Health, Munich, Germany
- Patrick Nolan, MRC Mammalian Genetics Unit, Harwell, UK
- Véronique Blanquet, Université de Limoges, Limoges, France
- Jean Jaubert, Institut Pasteur, Paris, France
- Mara Dierssen, Centre for Genomic Regulation, Barcelona, Spain
- Werner Müller, University of Manchester, Manchester, UK
- Antonio Baldini, Institute of Genetics and Biophysics CNR-IGB, Naples, Italy
- Xavier Warot, Ecole Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland
- Alan Hart, University of Edinburgh, Roslin Institute, Edinburgh, UK
- Petra Sipilä, University of Helsinki, Helsinki, Finland
- Paul Krimpenfort, Netherlands Cancer Institute, Amsterdam, Netherlands
- Jaime Carvajal, CSIC-CABD, Seville, Spain
- Mike Bowl, MRC Mammalian Genetics Unit, Harwell, UK
- BSRC Alexander Fleming, Vari - Athens, Greece
- CERBM-GIE, Strasbourg, France
- CNR, Monterotondo, Italy
- CNRS, France
- National Centre for Biotechnology, CSIC, Madrid, Spain
- EMBL-EBI, Hinxton, UK
- Helmholtz Zentrum München, Munich, Germany
- Instituto Gulbenkian de Ciência, Oeiras, Portugal
- Institute of Molecular Genetics ASCR, Prague, Czech Republic
- Karolinska Institute, Stockholm, Sweden
- MRC Harwell, Oxfordshire, United Kingdom
- Netherlands Cancer Insitute, Amsterdam, The Netherlands
- Sanger Institute, Hinxton, United Kingdom
- Tel Aviv University, Tel Aviv, Israel
- University of Oulu, Oulu, Finland
- University of Veterinary Medicine, Vienna, Austria
The EMMA network has been engaged in a number of infrastructure projects funded by the EC FP7 Capacities Specific Program and by previous EC Framework Programs. Furthermore, EMMA has been supporting other EC funded research projects such as EUMODIC, EUCOMM and its successor project EUCOMMtools. EMMA has also collaborated with the Wellcome Trust and the Sanger Institute Mouse Genetics Program. The projects EMMA is involved in lead to a significant growth of the EMMA archive in the coming years. Sustainable funding and the development of two complementary and linked infrastructure networks for large-scale and comprehensive phenotyping and archiving of mouse models have been addressed by the INFRAFRONTIER preparatory phase project. As a result the INFRAFRONTIER Research Infrastructure has been set up which runs the EC FP7 funded INFRAFRONTIER-I3 infrastructure project together with other National INFRAFRONTIER Partners. The INFRAFRONTIER Research Infrastructure also makes significant contributions to the global IMPC mouse phenotyping initiative. Global distribution of the mouse mutant lines stocked in EMMA is aided by the participation of the EMMA network in the Federation of International Mouse Resources (FIMRe).
To further develop and exploit the emerging mouse mutant resource, mouse models must be preserved and made available to the European biomedical research community. To this effect, the EC FP7 funded INFRAFRONTIER-I3 project brings together the European Mouse Mutant Archive (EMMA) network and the leading European centers for systemic phenotyping of mouse mutants. The INFRAFRONTIER-I3 partners aim to meet the future challenges presented by phenotyping, archiving and disseminating mouse models in the European Research Area as follows:
- Contribute to resource development by archiving of 1215 new mouse mutant lines
- Provide free of charge Transnational Access to mouse production and 1st line phenotyping capacities
- Offer a specialized axenic service to produce, maintain and to distribute germ-free mice
- Provide user friendly accession of INFRAFRONTIER services, extensive manual data curation and cross referencing with other mouse database
- Improve user services by developing novel phenotyping and cryopreservation SOPs and by refining innovative research instrumentation
- Engage with the user community using a wide range of PR activities, a dedicated user meeting and an industry liaison workshop
- Offer state of the art cryopreservation and phenotyping training courses
- Benchmark INFRAFRONTIER services with other major repositories
The comprehensive physical and data resources that will be generated by INFRAFRONTIER-I3 will contribute to link basic biomedical research to medical applications and thereby drive innovation and support the Europe 2020 Strategy.
The EMMAservice project was funded by the EC FP7 Capacities Specific Program from January 2009 until December 2012. The EMMAservice project was built on the achievements of its successful predecessor, the EMMAinf project that was funded by the EC FP6 Infrastructures Program. EMMAservice was an Integrated Infrastructure Initiative (I3) combining, in a closely co-ordinated manner: (i) Networking activities, (ii) Transnational Access and / or service activities and (iii) Joint research activities. All three categories of activities are mandatory as synergistic effects are expected from these different components.
Objectives of EMMAservice
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. Building on EMMA's previous achievements as the primary mouse repository in Europe, EMMAservice aimed to meet the future challenges presented by archiving and disseminating mouse models in the European Research Area as follows:
- Archiving of 1224 new mouse mutant lines in support of individual depositors and also European mouse genetics programs.
- Support of eligible customers with free of charge Transnational Access for up to 20% of requested mouse resources.
- Technology development to underpin the archiving and distribution efforts by advancing current sperm freezing technology.
- Training courses to promote the shipment of frozen germplasm rather than live mice.
- EMMA informatics to support user services by setting new standards for user friendly access to EMMA services, extensive data curation and cross referencing with other mouse database resources.
- Widening of outreach efforts to attract new users and directing efforts towards the translational research community.
EMMAservice contributed significantly to the development of a world leading repository and European capacity in mouse disease model archiving and distribution, supporting the needs of the wider European biomedical research community. The emerging mouse mutant and associated data resources offer the opportunity to decipher molecular disease mechanisms and may, in some instances, provide the foundation for the development of diagnostic, prognostic and therapeutic strategies.
For many years EMMA successfully collaborates with EUCOMM and now with the successor project EUCOMMtools. While EUCOMM vectors and ES cells are distributed by the European Mouse Mutant Cell Repository, mutant mice produced from the EUCOMM ES cell resource by the EUCOMM and EUCOMMtools projects are being distributed via the European Mouse Mutant Archive (EMMA).
- Generation, archiving, and world-wide distribution of up to 12.000 conditional mutations across the mouse genome in mouse embryonic stem (ES) cells
- Establishment of a limited number of mouse mutants from this resource
- Conditional gene trapping - random approach for expressed genes
- Conditional targeted trapping - directed approach, used for expressed genes
- Conditional gene targeting - directed approach, used for non-expressed genes
- Generation of European mouse functional genomics platform by synergistic integration of EMMA, EUMODIC, EURExpress, FLPFLEX ,FunGenES, PRIME and others
- Cornerstone of world-wide mouse mutagenesis effort, member of the International Knockout Mouse Consortium (IKMC)
- Improvement of health research
- Speed-up of drug development, therapy and diagnosis
- Competitive advantage for pharmaceutical industry
Funding & Structure
- Funded by European Union (FP 6, Priority 1 "Life Sciences, Genomics and Biotechnology for Health")
- EU funding: up to 13 million Euros
- Integrated Project
- Consortium: 9 participants from four European countries
"EUCOMMTools for Functional Annotation of the Mouse Genome" - is the successor project of EUCOMM and member of the International Knockout Mouse Consortium (IKMC)
- EUCOMMTOOLS will complete the IKMC resource of mutations for all protein coding genes
- EUCOMMTOOLS will maximize the utility of the conditional IKMC resource by generating up to 250 different, mostly inducible Cre driver mouse lines
- EUCOMMTOOLS will develop novel tools to enhance the versatility of the IKMC resource
- EUCOMMTOOLS vectors, mutant ES cells and mutant mice are distributed worldwide
- EUCOMMTOOLS mutant ES cells and vectors can be obtained from the European Mouse Mutant Cell Repository (EuMMCR)
The Wellcome Trust has negotiated and funded the acquisition of a limited number of gene knockout mouse strains and associated phenotypic data from Deltagen Inc. and Lexicon Pharmaceuticals. This resource was archived and is now being distributed through EMMA and provides researchers with unprecedented access to two private collections of knockout mice. These valuable models will not only aid the study of human disease but will also form part of a genome-wide library of knockout mice. Under the terms of the world-wide academic license granted to the Trust for the use of the mouse lines by Deltagen and Lexicon, researchers will be able to share the mouse lines acquired with other academic collaborators.
To assist the Wellcome Trust in tracking the outputs of the research to which it has contributed either wholly or in part, the Trust's contributions must be acknowledged in all publications according to the Trust's Guidance for Research Publication Acknowledgement Practice. EMMA customers must refer to the 'Wellcome Trust Knockout Mouse Resource'.
Two calls for proposals were published and a total of 87 lines were awarded. These lines were rederived and archived by EMMA and are freely available to the research community.
DELTAGEN STRAINS on the list of available EMMA strains
LEXICON STRAINS on the list of available EMMA strains