A Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination.
Even mice with the same autism gene can act very different, so check the exact behavior list before you plan treatment studies.
01Research in Context
What this study did
Scientists bred a new kind of mouse. It carries a Chd8 gene change linked to autism.
They recorded the adult mice’s ultrasonic squeaks. They also ran tests for motor skill, repetitive acts, and social interest.
What they found
The mutant mice made longer adult calls than typical mice.
They also showed better motor coordination on a rotating rod.
Surprisingly, the mice did not show extra repetitive moves or social problems.
How this fits with other research
Özcan et al. (2025) saw a different picture in human babies. After those infants learned to walk, their gestures and sounds did not grow together like in typical kids. The mouse and baby results seem opposite, but one is adult mice and the other is newly-walking infants. Species and age explain the clash.
Hudry et al. (2020) asked for better motor tools and long tracking. This mouse paper answers with exact rotor-rod scores and call length data.
Stewart et al. (2018) also counted mouse squeaks, but in Nf1 mutants. Both labs show that different gene changes shape calls in their own ways.
Why it matters
Chd8 mice do not all look alike. Some lines show social loss; this one shows strong paws and long calls. Before you pick a “Chd8 model” for drug work, open the behavior sheet. Match the model to the skill you want to fix.
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02At a glance
03Original abstract
Mutations in CHD8 are among the most common autism-causing genetic defects identified in human genomics studies. Therefore, many labs have attempted to model this disorder by generating mice with mutations in Chd8. Using a gene trap inserted after Exon 31, we created a novel Chd8 mutant mouse (Chd8+/E31T ) and characterized its behavior on several different assays thought to have face validity for the human condition, attempting to model both the core symptoms (repetitive behaviors and social communication impairments) and common comorbidities (motor deficits, anxiety, and intellectual disability). We found that Chd8+/E31T mice showed no difference compared to wild-type mice in amount of self-grooming, reproducing the negative finding most other studies have reported. Unlike some of the other published lines, Chd8+/E31T mice did not show deficits in the three-chamber test for social novelty preference. A few studies have examined ultrasonic vocalizations in Chd8 mutant mice, but we are the first to report an increase in call length for adult mice. Additionally, we found that in contrast to previous published lines, Chd8+/E31T mice displayed no anxiety-like behaviors or learning impairments but showed paradoxically significant improvement in motor function. The inconsistencies in behavioral phenotypes in the Chd8 mutant mice generated by different laboratories poses a challenge for modeling autism spectrum disorder and preclinical studies in mice going forward and warrants further investigation into the molecular consequences of the different mutations in Chd8 and the functional impact on behavior. LAY SUMMARY: Several different mouse models carrying mutations in the Chd8 gene have been created to study the effects of these autism-causing mutations in the laboratory. The current study characterizes a novel Chd8 mutant mouse model as well as summarizes data from previously published Chd8 mutant mice. The inconsistencies between different studies are concerning, but future research into the reasons why these inconsistencies occur may help us understand why patients with various mutations have different degrees of symptom severity. Autism Res 2020, 13: 1685-1697. © 2020 International Society for Autism Research and Wiley Periodicals LLC.
Autism research : official journal of the International Society for Autism Research, 2020 · doi:10.1172/jci.insight.92052