The German Mouse Clinic: A Platform for Systemic Phenotype Analysis of Mouse Models

Abstract

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.

A novel N‐ethyl‐N‐nitrosourea–induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model

“…Ali14/ϩ mice were analyzed intensively in a systematic phenotyping center, the German Mouse Clinic (28,29). After analyzing more than 240 parameters in this study, we found novel functions of Plcg2 in vivo.…”

Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers

“…−/− knockout mice, a total of 30 mutant and 30 control mice for each mouse line, were performed at the German Mouse Clinic using a standard battery of tests (Gailus-Durner et al 2005Fuchs et al 2009Fuchs et al , 2011 The detailed phenotypic analysis of the mice is described in Supplemental Data. A complete description of the methods can be found at the German Mouse Clinic website (http://www .mouseclinic.de).…”

Immune modulation by Fas ligand reverse signaling: lymphocyte proliferation is attenuated by the intracellular Fas ligand domain

“…Only the latter develop the lymphoproliferative disease and accumulate an aberrant CD3 ϩ B220 ϩ CD4 Ϫ CD8 Ϫ T-cell population and autoantibodies, while the remaining FasL killing capacity in gld,wt heterozygous mice is already sufficient to completely prevent gld-associated pathology. 4 Systemic first-line phenotyping at the German Mouse Clinic (GMC; 15,16 ) revealed that unchallenged homozygous FasL ⌬Intra mice do not display any phenotypic anomalies, exhibit normal T-and B-cell populations, no abnormality in Ig levels, and do not develop a gld-like lymphoproliferative disease (data not shown). The expression levels of Fas on the cell surface of lymphocytes are also normal (eg, see supplemental Figure 9A for T cells).…”