Functional studies and proteomics using transgene mouse models

Coordinator:    Prof. Dr. Andreas Zimmer
Institution: Institut für  Molekulare Psychiatrie, Universitätsklinikum Bonn
The goal of this subproject is the functional validation of susceptibility genes for bipolar disorder, unipolar disorder and schizophrenia identified through a genome-wide association approach, using genetically engineered mouse models. These mouse mutants will be comprehensively characterized using behavioral and molecular methods, including proteomics. This approach will validate genetic determinants of mental disorders identified within the IG. Moreover, it will provide models that closely meet clinical expectations and identify potential diagnostic biomarkers.
As a proof of concept, the subproject aims at the functional validation of the purinergic ligand-gated ion channel P2RX7 and D-amino-acid metabolic enzymes, which have been identified as associated with bipolar disorder, unipolar disorder and schizophrenia respectively. The project will make use of different lines of genetically engineered mouse mutants with the ultimate goal to validate these candidates as risk factors and diagnostic tools for the most relevant mental disorders.Biomarkers. Biomarkers are measures of biological parameters of disease. Mouse models that represent distinct human disease phenotypes have become the focus of many biomarker discovery efforts. Due to the more homogeneous genetic background this approach has clear advantages over the use of human specimens, which are plagued by a low “signal-to-noise-ratio”. Mouse models established by Profs. Zimmer and Wurst will be interrogated using a modern proteomics platform that involves metabolic labelling with stable isotopes and subsequent mass spectrometry analysis to identify protein expression differences. The identified candidate biomarkers will be further investigated in cerebrospinal fluid specimens from patients suffering from affective and neurological disorders.

Additional relevant Internet links:
The Biomarkers Consortium
Further Coordinators:
INTRANET (Members login)