Affective disorders and immunoneuronal plasticity: Studies on the function of WKL1, a novel candidate gene for bipolar affective and catatonic disorders
Project management at the University of Würzburg:
The discovery of the WKL1 gene resulted from the search for novel candidate genes for bipolar affective and catatonic disorders within the framework of the currently ongoing project. The first goal of the follow-up project is to shed light on the role of WKL1 in the fine-tuning of neuronal excitability and the principles that control functional expression of the human WKL1 gene with regard to its relevance of the altered structure of the WKL1 protein for synaptic plasticity during brain development and adulthood. In order to study neuroprogressive changes and neurodegenerative processes associated with the genetically altered function of the WKL1 protein in the mouse model, knockout strategies will be used. An integrated series of experiments will be performed in mice with a targeted disruption of the WKL1 gene in vivo and with mouse brain-derived primary neuronal and neuron-glia cultures, in order to analyze the development and functionality as well as neurodegeneration and regeneration of WKL1-expressing cells. In this context the regulatory interactions of various neuronal systems which participate in the pathogenesis and pathophysiology of severe affective and motor disturbances will be elucidated. Since the peripheral expression of WKL1 is restricted exclusively to immunocompetent cells, the function of WKL1 in the immune system will also be studied. Based on the mouse model for molecular mechanisms associated with affective and neuroprogressive/degenerative disorders, the new knowledge can directly be transferred to preclinical therapeutic research representing an important step toward a more effective treatment of bipolar affective and schizoaffective disorders.
Projekt period: from 05.1999 to 04.2004