Journal article

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

Abstract

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