Traditionally, knock-out mouse models of parkin, PINK1 or DJ-1 result in mitochondrial dysfunction [125] but do not develop the locomotor phenotype of parkinsonism, nigral neuronal loss or Lewy-body pathology; rather they have elevated dopaminergic tone due to deficits in D2 presynaptic regulation of release [126,127]. Here, PRKN is linked to Parkinsonism.