NGFN-PLUS

Characterization of genetic mouse models for Parkinson´s disease

Coordinator:    Prof. Dr. Wolfgang Wurst
Institution: Institut für Entwicklungsgenetik, Helmholtz Zentrum München
Homepage: http://www.helmholtz-muenchen.de/idg
Aim of this project is the in vivo analysis of LRRK2 and Pink-1 function, genes associated with parkinsonism. We established different mouse models representing the human genetic mutations in mice. All models were analysed in detail on the morphological, biochemical and behavioural level and identified modifications compared with changes in Parkinson’s patients.

All animal models analysed display minor, partly model-specific behavioural changes which are in accordance with the premotor symptoms of the respective human mutation carriers. A distinctive symptom in all models is a slight gait modification. In addition to this motoric changes the LRRK2- and Pink-1-knock out models exhibit abnormalities in their sense of smell. Further non-motoric symptoms concern changed anxiety-related and explorative behaviour. Furthermore, in collaboration with the German Mouse Clinic, these animals showed that the immune system and the glucose metabolism in a variety of models is impaired as a result of the mutation. These are first translational reliable indications of the existence of co-morbidity between the common diseases neurodegeneration, immune dysfunctions and diabetes.
Another important result was that proof of compensatory molecular mechanisms has been found in these mouse models, which could provide a basis for neuroprotective and preventive therapies in future.



Figure: Genetic mouse models for Parkinson´s Disease (PD) are subjected to different behavioural tests in order to detect behavioural deficits associated with motor and non-motor symptoms of PD. On the figure, a mouse successfully identifies an odour in an olfaction discrimination test.
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