To the editor: To overcome the bottleneck of standardized, comprehensive phenotyping1, 2 in mouse genetics, we established within the National Genome Research Network (NGFN), and in collaboration with the pan-European consortium EUMORPHIA, a unique mouse phenotyping center (German Mouse Clinic, GMC) with open access to the scientific community. The production of mutant mouse lines (MMLs) by gene knockout and transgenic technology or by mutagenesis generates a large collection of models for in vivo analysis of distinct gene functions, many of them potentially providing models for the study of human diseases3–6. But full and efficient use of this large resource is now hindered by shortcomings in the quality and extent of the phenotypic analysis. 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 facilities of the GMC were designed to provide an optimized specific pathogen–free (SPF) infrastructure with individual units (laboratories and adjacent mouse rooms) for each screen. The examinations comprise the following areas: allergy, behavior, clinical chemistry, dysmorphology, energy metabolism, eye development and vision, host-pathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, and pathology (Supplementary Fig. 1 online). Screens for cardiovascular analyses and steroid metabolism were recently implemented. Additional units are designated to accommodate guest scientists for collaborative work, especially for the transfer of standardized protocols to other laboratories. MMLs entering the GMC are first examined in a comprehensive and standardized primary screen (approximately 240 different parameters per individual mouse). Therefore, an innovative workflow had to be established, allowing a series of noninvasive tests on the same cohort of animals without major interferences between individual examinations. A single passage of a group of 30 mutant mice in comparison to the same number of age-and sex-matched littermate controls provides a detailed picture about the complexity of the MML-related phenotype. Up to 26 MMLs can be analyzed in the primary screen per year. In particular the permanent active collaborations among experts in different fields have turned out to be the key factor for the effective and interdisciplinary characterization of MMLs. Standard operation procedures for all tests in the primary screening have been established and validated, and the GMC has been running for more than one year at its full capacity. Our experiences confirm the feasibility of the general concept of high-throughput mouse phenotyping, and for almost all lines, even well-known MMLs, new phenotypes were identified (715 parameters were found to be altered in 23 MMLs).

The GMC is an open-access technology platform, allowing all scientists worldwide to submit their MMLs for comprehensive phenotyping. A web-based application procedure for mouse import was established. All experiments are performed on a collaborative basis between the mouse provider and the GMC. Additional information and a description of the application procedures are available (http://www. mouseclinic. de).