Autism Spectrum Disorder-Related Gene Deleted in Zebrafish

Figure 1: Top view of the fluorescently tagged scales, skeleton, and lymphatic system of a zebrafish using confocal microscopy.

Julia Chivu ’24

Autism-spectrum disorder-related gene deletion in fish may provide insight into autism spectrum disorder in humans. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impacts an individual’s communication, behavior, social skills, and learning abilities. GluN2B is an ASD-related gene expressed during early brain development that impacts social development. While there are many identified ASD-related genes, the GluN2B gene was studied because the deletion of this gene has shown to be lethal in rodents. Scientists from the Sirotkin Laboratory at Stony Brook University utilized the CRISPR-Cas9 system to observe the functions of the gene in zebrafish and the consequences of its deletion for the organisms. 
The CRISPR-Cas9 system is a genetic laboratory tool that can alter DNA. This new technology allowed the researchers to delete the GluN2B gene from zebrafish. After gene editing, a variety of behavioral tests and whole brain imaging scans were performed. The zebrafish species was used in this experiment because their GluN2B gene is very similar to the function and structure to that found in humans. In addition, zebrafish are highly social creatures and various ASD-associated genes can negatively impact their sociability. 
Although the manipulated fish lacked a crucial developmental gene, they learned how to capture prey, survived into adulthood, and had no issues capturing prey. The fish were also found to be fertile and had normal movement. It is known that zebrafish develop strong social preferences towards members of the same species early on in development. As expected, the experimental fish had reduced social preference. Additionally, the brain imaging tests showed that zebrafish with and without the gene had similar brain size and excitatory/inhibitory balance corresponding to neuronal signaling. 
Nevertheless, the brain scans did show that GluN2B-deficient zebrafish had a reduced inhibitory neuron marker in the subpallium portion of the brain. The subpallium region contains structures involved in emotion regulation, memory, and cognitive function. The brain scan results coincide with pre-existing findings of reduced inhibitory neurons found in many autism spectrum disorder patients. Such findings and further research related to this gene can help expand our understanding of the GluN2B gene in humans.  Additional experimentation on the developmental mechanisms in the brain can determine how this gene induces ASD phenotypes.

Works Cited: 
[1] J. Zoodsma, et al., Disruption of grin2b, an ASD-associated gene, produces social deficits in zebrafish. NIH National Library of Medicine, (2022).
[2] Image retrieved from: 

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