Early motor deficits, sleep dysfunction and reduction in dopaminergic neurons in a park7 -/- zebrafish larval model of Parkinson’s disease

Parkinson's Disease (PD) is the fastest-growing neurological disorder and only symptomatic treatment is available. Zebrafish are ideally suited for high-throughput screening of disease modifying drugs and mechanistic studies. Mutations in park7 are associated with early-onset familial PD. Additionally, altered levels and subcellular location of the park7 protein product (DJ-1) have been found in PD patients without known park7 mutations. Here, we show that larval park7 ^−/− zebrafish show reduced number of dopaminergic neurons and motor dysfunction, similarly to the 1-methyl-4-phenylpyridinium (MPP ⁺ )-induced PD model. Additionally, PD-associated prodromal symptoms, such as reduced sensory function, increased sleep latency and daytime sleepiness, were also observed in the park7 ^−/− , but not in the MPP ⁺ -induced PD model. The park7 ^−/− is the first stable genetic zebrafish model of Parkinson’s disease which shows both motor and non-motor symptoms, together with a reduction in dopaminergic neurons, at a larval stage. The model should therefore be highly valuable as a tool for PD related drug screening and mechanistic studies.