Dopamine D-2 Receptor Knockout Mice Develop Features of Parkinson Disease
Rogan B Tinsley, Chris R Bye, Clare L Parish, Angela Tziotis-Vais, Sonia George, Janetta G Culvenor, Qiao-Xin Li, Colin L Masters, David I Finkelstein, Malcolm K Horne
ANNALS OF NEUROLOGY | WILEY-BLACKWELL | Published : 2009
OBJECTIVE: This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic alpha-synuclein-containing cytoplasmic inclusion of Parkinson disease (PD). METHODS: Mice with targeted deletion of the dopamine D(2) receptor gene (D(2)R[-/-]) have higher striatal and nigral dopamine turnover and elevated oxidative stress. These mice were examined for evidence of histological, biochemical, and gene expression changes consistent with a synucleinopathy. RESULTS: LB-like cytoplasmic inclusions containing alpha-synuclein and ubiquitin were present in substantia nigra pars compacta (SNpc) neurons of older D(2)R(-/-) mice, and wer..View full abstract
This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia Project Grant (MKH), NHMRC CJ Martin Fellowship (CLP), Brain Foundations (RBT), and the Bethlehem Griffiths Research Foundation (RBT).