Sex-Specific Behavioral Features of Juvenile and Adult Haploinsufficient Scn2aFemale Mice, Model of Autism Spectrum Disorder.

Scientists studied female mice with a genetic change linked to autism to understand why autism appears more common in boys. They found that female mice showed milder autism-like behaviors than male mice, including being more social than normal, taking more risks when young, and having some memory difficulties as adults. This suggests girls and boys may show autism symptoms differently.

This study examined behavioral differences between male and female mice with Scn2a gene mutations, a model for autism spectrum disorder. Researchers tested juvenile and adult female mice using various behavioral assessments. Female mice showed milder autism-like features compared to males, including increased risk-taking in young mice, heightened sensitivity to cold, mild memory problems in adults, abnormally increased social behavior, and altered decision-making across both age groups. These findings support the male predominance observed in autism diagnoses and suggest that females may express autism-related traits differently than males, potentially through distinct biological mechanisms.

Results suggest females with autism may present with different behavioral patterns than males, potentially leading to underdiagnosis. Clinicians should consider sex-specific assessment approaches and recognize that increased sociability in females may mask underlying autism traits.

Sample size not reported. Single study using animal model may not fully translate to human autism. Limited detail on methodology and statistical analyses. Behavioral assessments may not capture full complexity of autism-related traits.

Genetic variants of the SCN2A gene, encoding the Na1.2 sodium channel, cause a spectrum of neurodevelopmental and epileptic disorders, and are among those that show the strongest association with Autism Spectrum Disorder (ASD). ASD has a male-bias prevalence, but several studies have proposed that female prevalence may be underestimated due to different symptomatic expression compared with males. However, it is unclear whether this is related to actual different pathological features or to greater masking abilities in females. Studies on Scn2amice, a model of SCN2A haploinsufficiency and ASD, have shown an age-dependent ASD-like phenotype attenuated at adulthood in males.

However, little is known about the behavioral features of Scn2afemale mice. We performed a battery of behavioral tests that are relevant for assessing ASD-like features, investigating juvenile and adult Scn2afemale mice. Our results demonstrate that female Scn2amice exhibit an overall milder phenotype than males, showing increased risk-taking in juveniles, hyper-reactivity to cold stimuli, and mild memory impairments in adults, abnormally increased sociability, and altered decision-making related behaviors in both juveniles and adults. Thus, this aligns with the male-biased prevalence of ASD and supports the existence of sex-specific phenotypic differences, potentially arising from distinct underlying pathophysiological mechanisms.

Both sexes should be investigated in studies of mouse models of ASD.