The MitoPark Mouse - an animal model of Parkinson's disease with impaired respiratory chain function in dopamine neurons.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by selective and progressive degeneration of dopamine neurons in the substantia nigra. While most cases are sporadic a few rare familial forms of PD have been described. Several lines of evidence indicate that mitochondrial dysfunction may be involved in the etiology of the disease. Genes found to cause familial Parkinsonism have been linked to mitochondrial function and toxins that inhibit the mitochondrial respiratory chain have been found to cause dopamine cell death. Furthermore, higher numbers of respiratory chain deficient dopamine neurons are found in patients with PD than in age-matched controls. The MitoPark mouse model of PD was designed to directly test the hypothesis that mitochondrial dysfunction in dopamine neurons can cause a progressive parkinsonian phenotype. By cell type-specific inactivation of mitochondrial transcription factor A, a protein essential for mitochondrial DNA expression and maintenance, dopamine neurons were rendered respiratory chain deficient. MitoPark mice recapitulate several features of PD in humans such as adult-onset degeneration of nigrostriatal dopamine circuitry; motor deficits that are ameliorated by L-DOPA administration; progressive course of phenotypic manifestations and neurodegeneration; and altered response to L-DOPA treatment dependent on disease stage. In this review we compare the MitoPark mouse to other genetic or toxin-based rodent models of Parkinson's disease.