Project Information

Why CREATE?

Targeted conditional somatic mutagenesis defines an entirely new scientific field, driven by internationally coordinated initiatives (EUCOMM, KOMP, NorCOMM) established for the systematic generation of conditional mouse mutants on a large scale.

The majority of these initiatives are committed to the production of mutant mouse ES cell lines, each of which carries an altered or "floxed" allele of a single gene. These mutant ES cell mutations can be readily transformed into mice using blastocyst injection, and the mutation activated by crossing the mouse bearing the floxed allele with a Cre recombinase driver strain to induce the mutation in spatially and temporally determined patterns.

Intricate conditional and inducible gene manipulation approaches have led to the generation of cell lineage- or developmental stage-specific alterations under temporal control. The vast number of Cre recombinase-expressing mouse lines - often referred to as "Cre-Zoo" animals - has greatly contributed to these accomplishments by allowing Cre recombinase to be expressed in specific cell types, in some cases in an inducible manner.

The full power of conditional mutant ES cell libraries and mice can therefore only be exploited with the availability of well characterised mouse lines expressing Cre-recombinase in tissue, organ and cell type-specific patterns, to allow the creation of somatic mutations in defined genes.

Although several privately curated and locally held databases currently provide a limited catalog of existing Cre driver strains, common problems are:
- These are not well integrated and often outdated, so that much of the field works by "word of mouth" to locate the necessary reagents for generating their conditional mutations.
- Published data on Cre driver mice from disparate groups do not always capture critical details such as the efficiency of recombination, cell and tissue specificity, or genetic background effects.

CREATE will address these combined shortcomings - inaccessibility to existing Cre driver strains, their incomplete characterisation, and an inadequate coverage of cell and tissue types in which they are active by enlisting major mouse stakeholders dedicated to collecting, integrating and curating, expanding and disseminating the currently scattered Cre driver mouse databases through a unified portal to provide the necessary structure for worldwide access to these critical resources.

Goals of CREATE

Disseminate extant information on Cre mouse resources through generation of an international CreZOO database with linkages that capture existing knowledge of Cre driver mouse genetic construction, background, expression pattern and activity according to a single set of standards.

Develop a roadmap for harnessing emerging technologies and methods for improving Cre-mediated recombination in vivo through targeted, intensive workshops and a dedicated Cre8 web portal.

Define the requirements of the mouse research community, by collecting information on new Cre driver expression patterns necessary for in-depth analysis of mutagenesis in different cell and tissue types through a CreExpress forum.

This Coordination Action will complement the major investment European Commission has recently made into Projects that make use of the mouse as a model organism (eg, EUCOMM, EUMODIC) and into database coordination as a mode of disseminating their results throughout the scientific community (CASIMIR). The international dimension of activities coordinated through CREATE will provide the opportunity for Europe to provide benchmarks for the rest of the world and ensure cross-talk between mutagenesis, phenotype and gene expression data.

The CREATE consortium represents a core of major European and international mouse database holders and research groups involved in conditional mutagenes.

Principal Investigator Affiliated Institute Country Description
Andras NAGY Mt. Sinai Hospital Canada Hosts the oldest Cre database (Cre-X-Mice), a key player in NorCOMM, the Canadian mouse mutagenesis initiative
Ewan BIRNEY EMBL-EBI UK European Bioinformatics Institute
Janan EPPIG Jackson Laboratory USA Holds Cre strains for MGI and IMSR
Nadia ROSENTHAL EMBL-MR Italy International mouse biology research center: EMBL-Monterotondo
Ramiro RAMIREZ-SOLIS Wellcome Trust Sanger Institute UK Involvment in EUCOMM and EUMODIC, hosting major mouse mutagenesis and phenotyping initiatives
Steve Brown MRC Mammalian Genetics Unit (MGU) UK The MGU is the leading partner in EUMORPHIA (European Union Mouse Research for Public Health and Industrial Applications), a pan-European project to improve our understanding of human physiology and disease by developing informative mouse models.
Vassilis AIDINIS BSRC Fleming Greece Hosts largest SPF mouse facility in Greece
Wolfgang WURST HMGU Germany Coordinates EUCOMM and German Gene Trap Consortium
Yann HÉRAULT GIE-CERBM France Dedicated database (MouseCre) targeting a wide array of tissues

In addition, CREATE has international advisors that will form the International Coordination Group (ICG), and will participate in CREATE-funded workshop.

Principal Investigator Affiliated Institute Country
A. Francis STEWART Technische Universitaet Dresden, BioInnovationZentrum Germany
Björn LÖWENADLER AstraZeneca R&D Sweeden
Colin FLETCHER NIH USA
Colin McKERLIE Toronto Centre of Phenogenomics Canada
Elizabeth SIMPSON CMMT, University of British Columbia Canada
Geoff HICKS Mammalian Functional Genomics Centre Canada
Hongkui Zeng Allen Institute for Brain Science USA
Martin HRABÈ DE ANGELIS HMGU, German Mouse Clinic Germany
Moira O'BRYAN Monash Institute of Medical Research and Australian Phenomics Network Australia
Nathaniel HEINTZ Rockefeller University USA
Yuichi OBATA RIKEN Japan