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798
Establishing a Mouse Model of NL3R617W-Associated Autism Spectrum Disorder for a Functional Study
Wei Gao1, Qiao Cai2, Xiaoming Ying2
1Children's Health Department, Hongkou District Maternal and Child Health Institution, 200000 Shanghai, China; Department of Pediatric, The First People's Hospital of Taizhou, 318020 Taizhou, Zhejiang, China.
Actas Espanolas De Psiquiatria
|March 12, 2025
Summary
A novel mouse model with the neuroligin-3 R617W mutation (NL3R617W) exhibits autism spectrum disorder (ASD) behaviors. This mutation impacts synaptic protein interactions, reduces excitatory synapses, and impairs social behaviors in mice.
Area of Science:
- Neuroscience
- Genetics
- Behavioral Science
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition.
- Synaptic gene mutations are linked to ASD, but the NL3 R617W mutation's behavioral impact is unknown.
- This study establishes and characterizes a mouse model for ASD using the NL3 R617W mutation.
Purpose of the Study:
- To create a mouse model of ASD using the NL3 R617W missense mutation.
- To investigate the molecular and behavioral characteristics of this NL3R617W mouse model.
- To understand how the NL3 R617W mutation affects synaptic function and behavior.
Main Methods:
- Immunofluorescence and Western blot to analyze protein expression and distribution.
- Confocal microscopy to quantify synapse numbers.
- Co-immunoprecipitation to study protein interactions.
- Behavioral tests including Morris water maze, Y maze, open field, and three-chamber test.
Main Results:
- NL3 R617W mutation affects NL3-NRXN1 interaction and inhibits VGluT1 expression.
- Mice with NL3R617W mutation show reduced spatial memory, exploration, and PSD95/SHANK3 expression.
- Significant reduction in excitatory synapses in the hippocampus and sensory cortex.
- NL3R617W mice display decreased activity and reduced social interaction with unfamiliar mice.
Conclusions:
- NL3 R617W mutation may inhibit postsynaptic scaffolding proteins via NRXN1 interaction.
- This leads to impaired synapse formation and a reduced number of excitatory synapses.
- The NL3R617W mouse model provides insights into ASD pathogenesis.
