Understanding the mechanistic basis of DA neuronal loss in mammalian models of PINK1 and Parkin has proved challenging, because it has been difficult to recapitulate a PD-like neurodegenerative phenotype in rodents, with the notable exceptions of mutant Parkin over-expression in mice and rats [59,60]; the Pink1-null rat model [61]; and exposure of Parkin-null mice to chronic mitotoxic stress [21]. This evidence concerns the gene PRKN and Parkinson disease.