PUBLICATION
Hyperactivity, Memory Defects, and Craniofacial Abnormalities in Zebrafish fmr1 Mutant Larvae
- Authors
- Hu, J., Chen, L., Yin, J., Yin, H., Huang, Y., Tian, J.
- ID
- ZDB-PUB-200213-5
- Date
- 2020
- Source
- Behavior Genetics 50(3): 152-160 (Journal)
- Registered Authors
- Hu, Jia, Tian, Jingjing
- Keywords
- CRISPR/Cas9, FMR1, FXS, Zebrafish
- MeSH Terms
-
- Animals
- Bone Development/genetics
- Clustered Regularly Interspaced Short Palindromic Repeats
- Craniofacial Abnormalities/genetics*
- Disease Models, Animal
- Female
- Fragile X Syndrome/genetics*
- Fragile X Syndrome/physiopathology
- Hyperkinesis/genetics*
- Larva/genetics
- Male
- Memory Disorders/genetics*
- Mutation
- RNA-Binding Proteins/genetics*
- RNA-Binding Proteins/physiology
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/physiology
- PubMed
- 32048109 Full text @ Behav. Genet.
Citation
Hu, J., Chen, L., Yin, J., Yin, H., Huang, Y., Tian, J. (2020) Hyperactivity, Memory Defects, and Craniofacial Abnormalities in Zebrafish fmr1 Mutant Larvae. Behavior Genetics. 50(3):152-160.
Abstract
Fragile X syndrome (FXS) is a heritable mental retardation disease caused by unstable trinucleotide repeat sequences in FMR1. FXS is characterized by delayed development, hyperactivity, and autism behavior. Zebrafish is an excellent model to study FXS and the underlying function of fmr1. However, at present, fmr1 function is mainly studied via morpholinos or generated mutants using targeting induced local lesions in genomes. However, both of these methods generate off-target effects, making them suboptimal techniques for studying FXS. In this study, CRISPR/Cas9 technology was used to generate two zebrafish fmr1 mutant lines. High-throughput behavior analysis, qRT-PCR, and alcian blue staining experiments were employed to investigate fmr1 function. The fmr1 mutant line showed abnormal behavior, learning memory defects, and impaired craniofacial cartilage development. These features are similar to the human FXS phenotype, indicating that the fmr1 mutant generated in this study can be used as a new model for studying the molecular pathology of FXS. It also provides a suitable model for high-throughput screening of small molecule drugs for FXS therapeutics.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping