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CL XII Mouse Model Systems of Inflammation

Summary

Multiple mutant mouse lines representing genes and pathways involved in acute and chronic inflammatory processes have been generated in the Cluster during the first funding period, which will provide unique entry points for functional pre-clinical studies in different RAs during the 2nd Cluster phase. Further, several Quantitative Trait Locus (QTL)-congenic strains, advanced intercross lines, and conplastic strains have been generated, distinct aspects of which will be tested in the different RAs. This laboratory is designed to standardize and further improve the use of genetically modified animals and provocation models of inflammatory diseases in the Cluster. First, the concept includes centralized housing and breeding in state-of-the art facilities in a specific pathogen free (SPF) environment as a prerequisite for the assessment of complex host-microbiota interactions. Secondly, the CL aims at setting up a mouse database system comprising genetic and immunologic information for each individual mouse line available in the Cluster. To gain such information, we will establish a centralized infrastructure to standardize genotyping and immunophenotyping. The latter will comprise a three-step program including determination of basic immune cell composition, assessment of immune cell function and evaluation of complex immune functions in experimental models of barrier diseases.

Contribution to the Scientific Discourse

Murine models of inflammation at (epithelial) interfaces play an important role for the functional understanding of disease mechanisms. This CL will create an integrated research structure between the participating institutions by: (1) standardization of genotyping, (2) SOPs for experimental models of selected barrier diseases, (3) data management infrastructure providing information on locally available genetically modified mice and experimental disease models within the Cluster, (4) standardized monitoring of microbiota composition in indicator strains at all locations (16s rDNA) and establishment of a limited gnotobiotic facility, and (5) a defined “immune-evaluation” strategy of genetically altered mouse lines. The CL serves as an instrumental partner of the universities in implementing long-term plans to modernize and reorganize the animal housing capacities in Schleswig-Holstein.

Figure:  Agenda of the CL to improve animal research and experimental disease models

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