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A new standard: Phenotyping in the German Mouse Clinic.

Vortrag: Mouse Molecular Genetics Meeting, 28th. August - 3rd September 2006, Cold Spring Harbor, USA. (2006)
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With the growing number of new interesting and valuable mouse mutants generated by various strategies (e.g. knock out, gene trapping or ENU-mutagenesis), the need for a comprehensive and standardized phenotypic characterization of these mouse models rises. A comprehensive analysis via a set of parameters relevant for many diseases will enable us to evaluate the potential power of these mouse models in order to further dissect biological pathways. The German Mouse Clinic (GMC), located at the GSF Research Centre in Munich, offers a comprehensive, standardized phenotype analysis of mouse mutants by specialists from various disciplines and from different institutions in Germany, working side by side at one place. The phenotypic screens focus on the areas of allergy, behavior, bone and cartilage, cardiovascular diseases, clinical chemistry, eye development and vision, energy metabolism, immunology, lung function, neurology, nociception, molecular phenotyping, steroid-metabolism, and pathology. Additional screens for host-pathogen interaction are performed at the GBF Research Centre in Braunschweig. The phenotypic analysis is performed on the basis of a scientific collaboration. In a primary screen, mice are analyzed for 240 key parameters of different pathways and organ systems. Parameters exhibiting conspicuous deviations in mutants compared to their controls will be followed up in more deep drilling secondary and tertiary tests. Within the European initiative EUMORPHIA, we have standardized and validated our screening procedure. In the near future, our centre will be part of the pan-European mouse phenotyping initiative EUMODIC. More than 50 mutant lines have been analyzed in the primary screen, and baseline data for 9 mouse inbred strains and hybrids are available. From the mutant lines, which comleted the primary screen, we found new or additional phenotypes in 47 mutant lines. At least subtle changes were detected in almost every mutant line. Secondary screens were recommended for 45 mutant lines. We will present data of the analysis of mouse models for human diseases e.g. data of a model for Down syndrome, osteogenesis imperfecta, and osteoarthritis. Our data contributed in these mutant lines either to the identification of the mouse lines as a model system for these diseases, or we added with our screening parameters further similarities of the mutant line to the human syndromes.   As a next step, we will include genotype-environment-interactions in the analysis of the mutant lines. We will switch from a constant to a variable environment by establishing “environmental platforms” with different standardized challenge experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences.
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Publication type Other: Lecture
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