Chd8 Deficiency in Zebrafish Causes Autism-Like Behavioral Deficits.

Scientists created a fish model of autism by changing a gene called Chd8 that is linked to autism in humans. The modified fish showed autism-like behaviors including problems with social interaction, anxiety, movement difficulties, and larger head size - similar to what's seen in people with autism who have changes in this same gene. This fish model could help researchers better understand autism and test new treatments.

This study established a zebrafish model of autism spectrum disorder (ASD) by disrupting the Chd8 gene, one of the most significant high-confidence ASD risk genes. Researchers comprehensively assessed behaviors in homozygous Chd8 mutant male zebrafish and found multiple autism-like characteristics including social deficits across shoaling, social interaction, and three-chamber preference tests. The mutants also displayed anxiety-like behavior, locomotor coordination problems, and macrocephaly (enlarged head size). These behavioral and physical features closely mirror symptoms observed in human patients with disruptive Chd8 mutations, establishing this zebrafish line as a robust animal model for investigating ASD mechanisms and screening potential therapeutic interventions.

Establishes a validated animal model for CHD8-related autism that could accelerate research into underlying mechanisms and therapeutic screening. May inform understanding of social behavior deficits and comorbid features in individuals with CHD8 mutations, potentially guiding targeted intervention development.

Sample size not reported. Study conducted only in male zebrafish. Behavioral characterization methods not detailed in abstract. No comparison with other ASD models or control interventions described. Long-term developmental outcomes not assessed.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic and environmental components. Despite progress made over the past decades, no effective therapies targeting the core symptoms of ASD are currently available. More research is required to explore the underlying mechanisms of ASD and discover potential therapeutic targets. Chromodomain helicase DNA-binding protein 8 () is one of the most significant high-confidence ASD risk genes identified to date.

However, the precise roles and mechanisms ofin neurodevelopment and behaviors remain incompletely understood. Zebrafish represent an emerging model organism for ASD research. While several zebrafish models withdisruption have been established, behavioral consequences have not been thoroughly characterized. Leveraging the high survival rate of homozygousmutant males, we comprehensively assessed their behaviors.

The mutants exhibited social deficits across multiple assays, including shoaling, social interaction and three-chamber social preference test. Additionally, anxiety-like behavior, locomotor coordination deficits, and macrocephaly were observed. These phenotypes closely resemble the symptoms in patients carrying disruptivemutations. Our findings establish thismutant zebrafish line as a robust model for investigating ASD pathological mechanisms and screening for potential therapies.