Hypoactivity, Abnormal Musculature, and Learning and Memory Defects in slc6a3 zebrafish Mutant Larvae

Abstract

Dopamine (DA) is one of the most common neurotransmitters in living organisms and is involved in the regulation of behavior, physiology, and disease. The dopamine transporter (DAT, encoded by the slc6a3 gene) re-uptakes dopamine from the synaptic cleft back into neurons, which plays a critical role in regulating dopamine signaling. Clinically, mutations in slc6a3 have been implicated in various diseases. Zebrafish are good model organisms for studying the functions of slc6a3 and dopamine. Work using the zebrafish slc6a3 mutant has previously been reported, but this mutant is not a complete loss-of-function mutant. In the present study, we knocked out the slc6a3 gene using CRISRP/Cas9 technology and obtained a zebrafish mutant with complete loss of function of slc6a3. Behavioral assessments and quantitative reverse transcription (qRT)-PCR revealed musculature injury, decreased activity, and decreased learning and memory ability in the slc6a3 mutant. This study provides a new theoretical basis for understanding the function of slc6a3 and provides a new model organism for studying the molecular pathology underscoring dopamine metabolism-related diseases. It also provides a suitable model for high-throughput screening of small-molecule drugs targeting slc6a3.