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Molecular Autism
Published in: Molecular Autism 1/2018

Open Access 01-12-2018 | Research

CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors

Authors: Chun-xue Liu, Chun-yang Li, Chun-chun Hu, Yi Wang, Jia Lin, Yong-hui Jiang, Qiang Li, Xiu Xu

Published in: Molecular Autism | Issue 1/2018

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Abstract

Background

Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique.

Methods

CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b −/− ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish.

Results

shank3b−/− zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish.

Conclusions

We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b−/− zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD.
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Metadata
Title
CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors
Authors
Chun-xue Liu
Chun-yang Li
Chun-chun Hu
Yi Wang
Jia Lin
Yong-hui Jiang
Qiang Li
Xiu Xu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2018
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-018-0204-x

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