Dopamine D2 receptor knockout mice develop features of Parkinson disease

Abstract

Objective: This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic α-synuclein-containing cytoplasmic inclusion of Parkinson disease (PD). Methods: Mice with targeted deletion of the dopamine D2 receptor gene (D2R[-/-]) 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 α-synuclein and ubiquitin were present in substantia nigra pars compacta (SNpc) neurons of older D2R(-/-) mice, and were also occasio..