PUBLICATION
Mutation of ube3a causes developmental abnormalities and autism-like molecular and behavioral alterations in zebrafish
- Authors
- Dougnon, G., Rummel, L., Matsui, H.
- ID
- ZDB-PUB-250911-5
- Date
- 2025
- Source
- Brain research bulletin : 111542111542 (Journal)
- Registered Authors
- Matsui, Hideaki
- Keywords
- RNA sequencing, autism, behavior, neurodevelopmental disorders, ube3a, zebrafish
- MeSH Terms
-
- Developmental Disabilities/genetics
- Behavior, Animal/physiology
- Mutation/genetics
- Autistic Disorder*/genetics
- Autism Spectrum Disorder/genetics
- Ubiquitin-Protein Ligases*/genetics
- Ubiquitin-Protein Ligases*/metabolism
- Animals
- Disease Models, Animal
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish/genetics
- PubMed
- 40930424 Full text @ Brain Res. Bull.
Citation
Dougnon, G., Rummel, L., Matsui, H. (2025) Mutation of ube3a causes developmental abnormalities and autism-like molecular and behavioral alterations in zebrafish. Brain research bulletin. :111542111542.
Abstract
Mutations in the UBE3A gene are responsible for neurodevelopmental disorders (NDDs), including Angelman syndrome (AS), which is characterized by developmental delays, impaired motor coordination, and cognitive disabilities. In recent years, UBE3A mutations have also been linked to autism spectrum disorders (ASD), due to their significant role in synaptic plasticity and cognitive function. Although substantial research has utilized mammalian models, the zebrafish (Danio rerio) provides unique opportunities to investigate gene functions owing to their transparent embryos, rapid development, and suitability for large-scale genetic and behavioral studies. In this study, we characterized a zebrafish model harboring a point mutation (T > A) in exon 3 of the zebrafish ube3a gene, which induces a stop codon resulting in a truncated protein. We performed comprehensive developmental, behavioral, and molecular analyses to investigate the impact of Ube3a dysfunction at both larval and adult stages. We observed alterations in embryonic development, significant locomotor deficits, including stereotypic movements, and reduced social preference and aggressiveness. Furthermore, RNA sequencing analysis of both larvae and adults revealed dysregulation in chromatin, nucleosome, protein-DNA, and primary cilia-related genes. Our findings provide a functional characterization of the ube3a mutation in zebrafish at both larval and adult stages. This zebrafish model offers new insights into the roles of UBE3A in neurodevelopment and behavior, expanding our understanding of its dysfunction in NDDs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping