Related Experiment Video
Updated: Dec 14, 2025
Author Spotlight: Exploring Autism Spectrum Disorder Symptoms in Fruit Flies — Genetic Models and Behavioral Tests
Published on: September 6, 2024
Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment
Emma J Mitchell1, David M Thomson1, Rebecca L Openshaw2
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.
Abstract:
There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment.
Insights
Mice with a 16p11.2 deletion model autism, showing stress-induced hyperactivity and reduced sociability. N-acetyl cysteine (NAC) and eletriptan treatments effectively normalized these autism-related behaviors in mice.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Autism Spectrum Disorder (ASD) lacks effective treatments despite its prevalence.
- 16p11.2 deletions are a significant genetic risk factor for ASD.
- Developing animal models is crucial for testing new therapeutic strategies.
Purpose of the Study:
- To investigate the behavioral phenotype of 16p11.2 deletion mice.
- To assess the therapeutic potential of N-acetyl cysteine (NAC) and eletriptan in an autism mouse model.
- To explore gene-environment interactions in ASD-related behaviors.
Main Methods:
- Ethological assessment of 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls.
- 24-hour home-cage monitoring of activity and social interaction.
- Administration of NAC and eletriptan to evaluate behavioral normalization.
Main Results:
- 16p11.2 DEL mice displayed normal behavior until stressed, then showed hyperactivity, reduced sociability, and anxiolysis.
- Both NAC and eletriptan significantly attenuated hyperactivity and reduced sociability.
- Neither NAC nor eletriptan reversed the anxiolytic phenotype.
Conclusions:
- 16p11.2 DEL mice exhibit an autism-relevant phenotype exacerbated by acute stress, highlighting gene-environment interactions.
- NAC and 5-HT1B/1D/1F receptor agonist (eletriptan) show promise for future autism treatment investigations.
- These findings support the utility of the 16p11.2 DEL mouse model for preclinical drug testing.
Related Concept Videos
02:27Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:20Gene-Environment Interactions
01:33Pleiotropy