Zebrafish as a Vertebrate Model Organism for Studying Movement Disorders

Zebrafish, Danio rerio , a subtropical vertebrate has, during the last decades, emerged as an important model organism in neurobiological and biomedical research. The zebrafish neurotransmitter systems, including major small molecular substances and neuropeptides and their receptors, are very similar with those of mammals. The small size of the fish at the time when active movement starts allows three-dimensional visualization of essentially all neurons, which contain specific markers. This allows detailed quantification of neurons of all important nuclei. This information can be correlated to fast kinematic analysis of, e.g., sensorimotor responses, and tracking of swimming episodes over longer periods of time. A large number of mutant fish with motor disturbances have been produced in genetic screens with alkylating agents and with retroviruses. Development of gene knock-out and transgenic fish has also become possible with TILLING or zinc finger nuclease methods. The easiest methods to modify gene expression include morpholino-modified oligonucleotides, which enable translation inhibition at best for several days. This method requires stringent controls and knowledge of non-specific off-target effects, which are common. Several genes that cause autosomal hereditary Parkinson’s disease have been identified and inactivated in zebrafish. The effects range from very mild to severe, some of which are likely non-specific. Well-controlled studies have given valuable information of basic functions of genes important in Parkinson’s disease and other human neurological diseases. The emergence of advanced gene modification methods, most obviously the gene knock-out and transgenic methods, is about to render zebrafish a very fast, quantifiable, and economic model to reveal basic functions of genes important for human neurological diseases.