New models for bone and cartilage related disorders and new ways of mouse models characterization.

Mouse model production and their systemic characterization are bottlenecks in the process of proper understanding of molecular mechanism in diseases. We have undertaken in the Munich ENU-Mouse Mutagenesis Screen a large-scale and genome wide production of mouse models for inherited human diseases. The new main focus is on bone and cartilage diseases. Bone densitometry, blood screens for bone parameters and turnover markers have been implemented in the F1 screen. We have isolated 16 new mouse models in different fields of bone and cartilage disorders. To appreciate the fact that many genes show pleiotropic effect we established a unique mouse phenotyping center (German Mouse Clinic, GMC). In the GMC, experts from various fields of mouse physiology and pathology in close cooperation with clinicians work side by side at one location The examinations comprise the following areas: bone and cartilage, allergy, behaviour, clinical chemistry, cardiovascular analyses, energy metabolism, eye development and vision, host-pathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, steroid metabolism and pathology. The systemic characterization of the new mouse models in the GMC has revealed the syndromic character of many bone related disorders. Data will be presented from the analysis of mouse models for 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 discovered further similarities of the mutant line with the human syndromes. We are currently implementing new challenge experiments for genotype-environment-interactions in the analysis of the mutant line. “Environmental platforms” are tested with different standardized challenge experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences