PUBLICATION

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

Authors
Liu, C.X., Li, C.Y., Hu, C.C., Wang, Y., Lin, J., Jiang, Y.H., Li, Q., Xu, X.
ID
ZDB-PUB-180406-5
Date
2018
Source
Molecular autism   9: 23 (Journal)
Registered Authors
Liu, Chunxue
Keywords
ASD, Animal model, CRISPR/Cas9, Social behavior, Zebrafish, shank3
MeSH Terms
  • Animals
  • Autistic Disorder/genetics*
  • Autistic Disorder/physiopathology
  • CRISPR-Cas Systems*
  • Disease Models, Animal*
  • Homer Scaffolding Proteins/genetics
  • Homer Scaffolding Proteins/metabolism
  • Locomotion
  • Mutation
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Social Behavior
  • Synaptophysin/genetics
  • Synaptophysin/metabolism
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
29619162 Full text @ Mol Autism
Abstract
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.
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.
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.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes