Animal models are crucial in the mechanistic study of Parkinson's disease and therapeutic development. However, a severe and unfortunate roadblock is that to date no genetic mammalian models have recapitulated the cardinal PD pathology of dopaminergic neuronal death in substantia nigra. To overcome this prominent obstacle and leave no stone unturned, we propose to take advantage of the different biology between mouse and rat, and to establish bacterial artificial chromosome (BAC) transgenic pre-clinical models for alpha-synuclein (Park1) and LRRK2 (Park8), two disease genes for autosomal dominant Parkinson's diseases. If these pre-clinical models have dopaminergic neuronal death in substantia nigra, they will be invaluable tools for this research field.
Dr. Li successfully generated BAC transgenic rats expressing wild-type and mutant alpha-synuclein or LRRK2. In follow-up studies he is working to complete the neuropathological characterization of these models.