Developmental pyrethroid exposure and age influence phenotypes in a Chd8 haploinsufficient autism mouse model.

Researchers studied mice with a genetic change linked to autism and exposed them to a common pesticide. The mice already showed autism-like behaviors such as increased anxiety and social difficulties. When exposed to the pesticide, their anxiety became worse. This suggests that children with certain genetic risks for autism might be more vulnerable to environmental factors like pesticide exposure, potentially worsening autism traits.

This mouse model study investigated how pesticide exposure affects autism-like behaviors in mice with Chd8 gene mutations, a known autism risk gene. Researchers exposed Chd8 haploinsufficient mice to deltamethrin pesticide from conception through early life. The mutant mice showed autism-associated behaviors including anxiety and altered social behavior. Pesticide exposure worsened anxiety-like behaviors in the mutant mice, demonstrating a gene-environment interaction.

The study identified specific genes consistently altered across different ages and found age-related changes in brain cells. Results suggest that genetic vulnerability combined with environmental pesticide exposure may exacerbate autism-related phenotypes, highlighting the importance of studying gene-environment interactions across the lifespan in autism research.

Results suggest individuals with Chd8 mutations may be more vulnerable to environmental pesticide exposure, potentially worsening autism symptoms. Supports need for environmental risk assessment in genetically vulnerable populations and highlights importance of studying autism across the lifespan.

Animal model study with unclear sample size reporting. Findings may not directly translate to humans. Single pesticide tested. Limited to one genetic mutation (Chd8). Behavioral outcomes limited to anxiety and social measures.

Hundreds of genes have been associated with autism spectrum disorder (ASD), including loss-of-function mutations in chromodomain helicase DNA binding protein 8 (Chd8). Environmental factors also are implicated in autism risk and have the potential to exacerbate phenotypes in genetically sensitized backgrounds. Here we investigate transcriptional and behavioral phenotypes in a Chd8 haploinsufficient (Chd8) mouse line exposed to the pesticide deltamethrin (DM) from conception to postnatal day 22. Vehicle-exposed Chd8mice displayed ASD-associated phenotypes, including anxiety-like behavior and altered sociability, replicating a previous study with this mouse line.

A core set of genes was altered in Chd8mice at multiple ages, including Usp11, Wars2, Crlf2, and Eglf6, and proximity ligation data indicated direct binding of CHD8 to the 5' region of these genes. Moreover, oligodendrocyte and neurodegenerative transcriptional phenotypes were apparent in 12 and 18 month old Chd8mice. Following DM exposure, the mutant mice displayed an exacerbated phenotype in the elevated plus maze, and genes associated with vascular endothelial cells were downregulated in the cerebral cortex of older Chd8animals. Our study reveals a gene x environment interaction with a Chd8 haploinsufficient mouse line and points to the importance of investigating phenotypes in ASD animal models across the lifespan.