In the German Mouse Clinic (GMC) the approach of a semi-biased molecular phenotyping screen for the identification of transcriptional changes in affected organs is used complementary to ‘classical’ phenotyping. We present an overview of the results of 46 mutant mouse lines (MMLs) analysed in the first three years and demonstrate the efficiency of genome-wide molecular phenotyping analysis. We have systematically assessed transcript profiles of 17 distinct organs of one adult stage using a microarray containing 21000 cDNA-probes. Samples for gene expression profiling are individually selected based either on conspicuous phenotypes in at least one of 14 GMC phenotype screens or on previous knowledge of the mutant phenotype. They are analysed in quintuples for each submitted MML. Microarray experiments were performed to analyse expression patterns of 90 organs from 46 MMLs, identifying up to 232 differentially expressed genes in 45 organs of 26 MMLs.
In our study we demonstrate that the strategy of selecting of affected organs for expression profiling analysis was highly efficient for the identification of gene regulation. There are numerous regulated genes detected in the analysed MMLs that were identified by our screen but not previously known to be involved in the phenotypical changes at the molecular level. In addition, synexpression groups of co-expressed genes in the same organ type of distinct MMLs were identified. However, the functional overlap of the co-expressed genes within these groups was rather low. The semi-biased gene expression profiling approach will be continued, focussing on the detailed analyses of functional annotations and cellular pathways of co-expressed genes in apparently un-related mutant strains.