Molecular Phenotyping Screen

Coordinator:    PD Dr. Johannes Beckers
Institution: Institut für Experimentelle Genetik, Helmholtz Zentrum München
The goal of the molecular phenotyping screen is the molecular description of models for human diseases. Expression profiling analysis in the primary screen is performed using commercial, whole-genome microarrays. We archive spleen, kidney, liver, heart, thymus, skeletal muscle, brain, and pancreas from mutant and control mice. For the analysis organs are selected based on conspicuous phenotypes in other GMC screens or on previous knowledge of predicted gene function or affected organs. Additionally, analysis of mouse lines after environmental challenges is performed. Statistical analysis is performed for the identification of significant differences in gene expression and their functional annotations of regulated genes are analysed.

Summary of selected major results:

(1.) In three knockout mouse models (Hmgn1, Hmgn3, Hmgn5) the functional redundancy of genes of the high mobility group N, playing a role as structure proteins in transcription, replication and DNA-repair, was analyzed.  Our analysis of brain, liver, spleen and thymus revealed, only a limited number of tissue- and mutant-specific regulated genes in the three mutant lines. These results indicate very specific functional effects of each of these Hmgn genes.

 (2.) The influence of a treatment with rapamycin and spermidine on life span and health of mice was analyzed. In both studies we observed that treatment with these agents restore - at least partly - aging-associated changes in the analyzed organs brain, heart, spleen and kidney. While for rapamycin the mechanism of activity using the mTor signal transduction pathway is already known, the data of the spermidine study might contribute to the detection of the still unknown target pathways for this agent.

Fig. 1: Heatmap Expression              Fig.2: Network Expression

Additional relevant Internet links:
The German Mouse Clinic
Further Coordinators:
INTRANET (Members login)