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Innovative mouse models for functional genomics in immunology

Final Activity Report Summary - IMDEMI (Innovative mouse models for functional genomics in immunology)

It becomes clear for an increasing number of diseases that chronic inflammation contributes substantially to the pathogenesis. The inflammatory process is controlled by the immune system which, under normal conditions, protects against infectious diseases. Therefore, better understanding of the pathogenicity of an immune response is required for the development of an effective therapy for many different diseases.

In the functional analysis of human diseases and the role of the immune system therein, mouse models proved to be very informative. Recent developments improved these mouse models considerably, not only on the level of genetic modification, e.g. conditional Knockout (KO) mice, but also in phenotypic analysis, e.g. in vivo imaging. On the other hand, the number of time and labour-consuming steps required for the generation of these models was substantially increased, as was the risk that the models would not fulfil the relevant high expectations at the end. Moreover, combinations of various transgenic and KO mouse strains were usually required to unravel only one particular aspect of a disease process. Therefore, progress in understanding human diseases would substantially accelerate by improving the efficacy and success rate of the generation of genetically modified mouse models and their phenotypic analysis in the context of a coherent research network.

The Marie Curie Research Training Network IMDEMI created an optimal scientific and technological environment for the development of novel genetically modified mouse strains, e.g. transgenic and KO mice, and the training of young researchers with an extensive exchange of knowhow, appointed researchers, mice and relevant scientific material. This was feasible through the foundation of a platform of four laboratories with state of the art technology and experience in the generation of innovative mouse models with a focus on immunology, surrounded by eight research groups with state of the art technology and experience in the phenotypic analysis of genetically modified mice and their application in a large variety of human disease models.

As a result, during a four years’ period, the generation of 14 different KO and transgenic mouse strains was completed for genes which play a key role in different aspects of inflammatory processes. Many of these KO and transgenic mouse strains were studied in disease models, such as Inflammatory bowel disease (IBD), arthritis, atherosclerosis, a model for Multiple sclerosis (MS), Systemic lupus erythematosus (SLE), cancer etc., resulting in new insights in the complex role of these target genes in the disease process. At the same time, 26 young researchers, i.e. 17 Early-stage researchers (ESRs) and 9 Experienced researchers (ERs), were extensively trained.

The IMDEMI network provided to the scientific community a cohort of innovative mouse models, e.g. conditional KOs, cell type specific Cre transgenic mice, cell type specific reporter mice, cell ablation models etc., and improved disease models such as IBD or acute lung failure. The network activities attracted the attention of both the Industry and the scientific community, resulting in direct collaborations between network participants and biotech companies and the participation of world leading experts in immunology to IMDEMI network symposia. Most importantly, a group of young researchers obtained a solid basis for a successful career in both academic and industrial research.