The German Mouse Clinic: a platform for systemic phenotype analysis of mouse models.

The German Mouse Clinic (GMC) is a large scale phenotyping center where mouse mutant lines are analyzed in a standardized and comprehensive way. The result is an almost complete picture of the phenotype of a mouse mutant line--a systemic view. At the GMC, expert scientists from various fields of mouse research work in close cooperation with clinicians side by side at one location. The phenotype screens comprise the following areas: allergy, behavior, clinical chemistry, cardiovascular analyses, dysmorphology, bone and cartilage, energy metabolism, eye and vision, host-pathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, steroid metabolism, and pathology. The German Mouse Clinic is an open access platform that offers a collaboration-based phenotyping to the scientific community (www.mouseclinic.de). More than 80 mutant lines have been analyzed in a primary screen for 320 parameters, and for 95% of the mutant lines we have found new or additional phenotypes that were not associated with the mouse line before. Our data contributed to the association of mutant mouse lines to the corresponding human disease. In addition, the systemic phenotype analysis accounts for pleiotropic gene functions and refines previous phenotypic characterizations. This is an important basis for the analysis of underlying disease mechanisms. We are currently setting up a platform that will include environmental challenge tests to decipher genome-environmental interactions in the areas nutrition, exercise, air, stress and infection with different standardized experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences.

Standardized morphological phenotyping of mouse models of human diseases within the German Mouse Clinic.

Inbred strains are the raw material for the generation of Genetically Engineered Mice (GEM) that have become indispensable tools for cancer research, and for the identification of genes involved in human diseases. The "German Mouse Clinic" was designed to provide the scientific community with a systematic, standardized and comprehensive phenotyping of mouse models on various genetic backgrounds and generated by different methods (transgenic, knockouts, ENU mutagenesis screen and gene-trap approaches). The pathology screen within the German Mouse-Clinic was conceived to ensure a complete morphologic phenotype of mouse models, to support discovery of genes functions, and to understand how these genes influence the development of human diseases. The goal is to define disease entities that can be recognized by a pathologist and relate them to human disorders when possible. Knowing the inherent morphologic phenotype of the most frequent used mouse strains is of utmost importance for the correct interpretation of mouse models. The main challenges, which pathologist are confronted to validate mouse models for human diseases include (1) knowledge of mouse biology and of histological differences between mouse strains and humans, (2) the terminology that should be used for the classification of neoplastic lesions in GEM's, (3) to asses the usefulness of a particular GEM as model for a human disease.