PUBLICATION
Knockout of tanc2 causes autism-like behavior and sleep disturbance in zebrafish
- Authors
- Long, F., Zheng, J., Zhou, J., Hu, P., Xiong, B.
- ID
- ZDB-PUB-221220-11
- Date
- 2022
- Source
- Autism research : official journal of the International Society for Autism Research 16(3): 524-534 (Journal)
- Registered Authors
- Xiong, Bo
- Keywords
- autism spectrum disorder, behavior, neurodevelopment, tanc2, zebrafish
- MeSH Terms
-
- Adult
- Animals
- Autism Spectrum Disorder*/genetics
- Autism Spectrum Disorder*/metabolism
- Autistic Disorder*/genetics
- Autistic Disorder*/metabolism
- Brain/metabolism
- Disease Models, Animal
- Neurons/physiology
- Proteins/metabolism
- Zebrafish/metabolism
- PubMed
- 36534563 Full text @ Autism Res
Citation
Long, F., Zheng, J., Zhou, J., Hu, P., Xiong, B. (2022) Knockout of tanc2 causes autism-like behavior and sleep disturbance in zebrafish. Autism research : official journal of the International Society for Autism Research. 16(3):524-534.
Abstract
Tanc2 is a large multi-domain postsynaptic scaffold protein mainly expressed in the brain. In humans, tanc2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders. However, the role of tanc2 in neurodevelopment and in controlling behaviors are not fully understood. Here, we generated and characterized a tanc2 knockout allele in zebrafish. Loss of tanc2 increases the larval brain size and body length by promoting proliferation and inhibiting apoptosis. We observed that the glutamatergic neuron population is significantly increased in tanc2 mutants while the GABAergic and the glycinergic neurons are not affected, suggesting that an excitatory/inhibitory (E/I) imbalance. Indeed, the tanc2 knockout larvae exhibited increase sleep. In adult zebrafish, the mutants display anxiolytic-behavior, reduced aggression, and impaired social preference. The alterations in these behaviors are phenotypically similar to the ASD patients carrying tanc2 mutations. Therefore, the tanc2 knockout allele could serve as a valuable model to further study the role of tanc2 in the nervous system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping