A G309D-Pink1 knock-in mouse model of the PARK6-form of Parkinson's disease

• Applicant: Dr. Suzana Gispert-Sánchez
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 18857684

To understand the pathogenesis of Parkinson¿s disease (PD) we have previously characterized genetic mouse mutants, where toxic alpha-synuclein leads to abnormal dopamine homeostasis and neurodegeneration. Now we have identified PINK1 as a potential protective factor of dopaminergic neurons through the study of a PD family and their tissues, where a G309D-PINK1 mutation causes the disease. Since mutant brain tissue is unavailable, we aimed to model this PD form (PARK6) in mice through a knock-in strategy and have generated such mice. At different ages the mice will be assessed for typical features of PARK6 patients: the clinical signs of PD will be monitored in behaviour tests; neuron populations known to degenerate in PD will be studied with histopathological and immunocytochemical techniques; markers of dopamine neurotransmission and oxidative stress will be investigated in neurochemical assays; furthermore, the brain tissue will be used to analyse the protein interactions of G309D-Pink1. Thus we hope to define criteria and molecules which will be crucial to validate neuroprotective approaches in the treatment of Parkinson¿s disease.

• DFG Programme: Research Grants