IG German Mouse Clinic - Deciphering Comorbidity in Human Disease Models

As a unique national resource we have established a platform for systemic, standardized phenotyping, the German Mouse Clinic (GMC), within the NGFN. In the GMC, experts from various fields of mouse physiology and pathology in close cooperation with clinicians work side-by-side at one location. Scientists from the Universities of Marburg, Bonn and Heidelberg, the Ludwig-Maximilians-University and the Technical University Munich, and the Helmholtz Zentrum München (HMGU) work in the GMC where the comprehensive primary screen is performed. In the GMC we offer a detailed characterization and interpretation of mouse models in a primary screening of more than 550 parameters in the areas of behavior, bone and cartilage, neurology, clinical chemistry and hematology, eye development, immunology, allergy, steroid metabolism, energy metabolism, lung function, vision, pain perception, gene expression and pathology. More than 520 additional parameters can be measured with secondary and tertiary screening methods. The latest techniques and technologies, including non-invasive in vivo imaging methods as well as informatics tools to handle the phenotype data, are used. In collaboration with more than 40 institutions in Germany and partners world-wide we have analysed more than 200 mouse models in the primary screen and published results of models from different disease areas (www.mouseclinic.de/results; www.mouseclinic.de/news). For example, the analysis of young CLN3 mice, a model for juvenile neuronal lipofuscinosis (JNCL), revealed new early phenotypes (altered blood parameters and sensory/behavorial phenotypes) that can serve as a basis for the development of new biomarker tools for pre-clinical and clinical use (Staropoli et al., 2012). In a new mouse model for Osteogenesis imperfecta (OI) we were able to show for the first time that the Aga2 mutation in type I collagen directly causes pathological changes in heart and lung tissue that are bone-independent and are the primary cause of death in affected Aga2 mutants (Thiele et al., 2012).

In order to identify genetically determined phenotypes dependent on environmental factors, we have set up challenge platforms focusing on major environmental risk factors for human health (German Mouse Clinic II, GMC II). We have chosen five areas – diet, air, stress, exercise and immunity – representing the major interfaces of the organism with the environment (gut, lung/skin, brain/sense organs, muscle/bone and immune system). For the different platforms, we implemented defined challenge test conditions for phenotypical analyses. For example, the systemic analysis of the mouse model for the Neurobeachin (Nbea) gene showed differences in body weight. Diet challenge experiments revealed an unexpected function of energy balance and body mass regulation for the Nbea gene. Furthermore, SNPs of Nbea were found to be associated with higher BMI in two human cohorts (Olszewski et al., 2012).

To ensure the exploitation of mouse models in the long run, it is essential to make them accessible to every laboratory within the scientific community. Therefore, valuable mutants have been preserved for the scientific community by archiving in the European Mouse Mutant Archive (EMMA) under the highest quality standards.

Latest results can be found in detail in the descriptions of the subprojects.