摘要：SummaryBrain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed inbdnf−/−compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a,clock1aandclock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms inbdnf−/−larvae. The circadian behavior was partially rescued by pharmacological treatment. Thebdnf−/−zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental diseasesGraphical abstractDisplay OmittedHighlights•Generation of a viablebdnfKO line in zebrafish•Bdnf deficiency affects locomotor activity and thigmotaxis in larvae•Differential RNA-seq analysis shows changes in expression of circadian clock genes•Bdnf mutant fails in the generation of the behavioral circadian rhythmicityBehavioral neuroscience; Molecular neuroscience; Developmental neuroscience; Cellular neuroscience
