PUBLICATION
Deficiency of KMT2D causes autistic-like behavior in mice and zebrafish
- Authors
- Shangguan, H., Huang, J., Wei, X., Huang, J., Cao, Z., Chen, X., Yuan, J., Zhang, J., Ye, B., Yan, R., Chen, R., Tao, W.
- ID
- ZDB-PUB-250830-12
- Date
- 2025
- Source
- Communications biology 8: 13111311 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Autistic Disorder*/genetics
- Behavior, Animal*
- DNA-Binding Proteins*/deficiency
- DNA-Binding Proteins*/genetics
- Disease Models, Animal
- Hippocampus/metabolism
- Histone-Lysine N-Methyltransferase
- Male
- Mice
- Mice, Knockout
- Myeloid-Lymphoid Leukemia Protein
- Social Behavior
- Zebrafish
- Zebrafish Proteins*/deficiency
- Zebrafish Proteins*/genetics
- PubMed
- 40883562 Full text @ Commun Biol
Citation
Shangguan, H., Huang, J., Wei, X., Huang, J., Cao, Z., Chen, X., Yuan, J., Zhang, J., Ye, B., Yan, R., Chen, R., Tao, W. (2025) Deficiency of KMT2D causes autistic-like behavior in mice and zebrafish. Communications biology. 8:13111311.
Abstract
Kabuki syndrome type 1 is a congenital multisystem disorder caused by KMT2D mutations. While some studies suggest that KMT2D deficiency may lead to autistic-like behaviors, the role of KMT2D in social behavior remains unconfirmed due to a lack of animal model evidence. In this study, we developed a mouse knockdown model and a zebrafish knockout model to investigate the role of KMT2D in synaptic function and behavioral patterns. We also performed an RNA sequencing analysis to delve into the molecular and cellular mechanisms of KMT2D. Results showed that Kmt2d deficiency in mouse and zebrafish both exhibited autistic-like behaviors including social behaviors defects and repetitive behavior. Additionally, knockdown of Kmt2d in the mouse hippocampus decreases excitatory and increases inhibitory synaptic transmission, disrupting the excitation-inhibition balance-a hallmark of autistic-like behaviors. RNA sequencing analysis revealed that under conditions of low kmt2d expression, differentially expressed genes were associated with glutamatergic and GABAergic synapses, supporting the dysregulation of excitation-inhibition balance in the hippocampus. Taken together, our research elucidates the critical role of KMT2D in modulating animal social behavior, potentially through its impact on synaptic excitation-inhibition balance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping