Parkinson's disease is the second most common neurodegenerative disease affecting the elderly. The movement disorder is caused by progressive loss of dopamine producing neurons. Loss of function mutations in the DJ-1 gene have been linked to early-onset familial parkinsonism, which clinically resembles Parkinson's disease. We propose that DJ-1 is required for the normal function and survival of dopamine producing neurons. Here we employ a mouse genetic approach to investigate how loss of DJ-1 function causes death of dopamine producing neurons through the generation and analysis of mutant mice lacking DJ-1. We will determine whether loss of DJ-1 function results in progressive loss of dopamine producing neurons and whether DJ-1 mutant mice exhibit motor deficits. We will also study whether DJ-1 plays important roles in dopamine neurons and the mitochondria. These studies will provide insights into disease causing mechanisms associated with DJ-1 mutations, and may help to design novel therapeutic strategies to combat this debilitating disease.