P.19.3 Phenotypic characterization of the autosomal recessive (Pink-1 and DJ-1) gene knockout rat models of Parkinson’s disease

Recessively inherited loss-of-function mutations in the DJ-1 or PINK1 gene are linked to familial cases of early-onset Parkinson’s disease (PD). Single-knockout mice (lacking either DJ-1 or PINK1) exhibit disruptions of dopamine homeostasis but no nigral dopaminergic degeneration. As part of the strategy to provide more tools for the research community, the MJ. Fox Foundation for Parkinson’s Research (MJFF) has funded the generation of novel rat models lacking either DJ-1 or PINK1 genes and sponsored a standardized characterization including behavioral, neurochemical and pathological measures to determine if these rats exhibit progressive PD-like phenotype. In the presentation, we will discuss PINK1 KO rats motor dysfunction and gait impairment compared to wild-type rats (WT) up to 8-months of age. The DJ-1 KO rats expressed similar motor and gait abnormalities, however these deficits were less pronounced and appeared mostly between 6 and 8 months of age. Characterizations of alpha-synuclein immunoreactivity and other biomarkers levels in these rat models are currently ongoing. These preliminary data demonstrate that loss of either the PINK1 or the DJ-1 gene in rats produces a progressive loss of dopaminergic neurons, and that this neurodegeneration may be correlated to progressive motor and gait deficits. Thus, these MJFF-generated Pink1 and DJ-1 knockout rats will help elucidate the mechanisms by which these recessive genes produce PD pathology and aid in therapeutic development.