Cognitive behavioral phenotyping of heterozygosity as a model for autism spectrum disorder.

UNLABELLED

It is estimated that 1 in 36 children are affected by autism spectrum disorder (ASD) in the United States, which is nearly a twofold increase from a decade ago. Recent genetic studies have identified loss-of-function (dnLoF) mutations in the as a strong risk factor for ASD. Previous research has shown that ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent underexpression captures the full range of behaviors, specifically cognitive phenotypes, presented in ASD. Here, we conducted a comprehensive cognitive behavioral phenotyping which revealed that loss of one copy of , as in the +/- mice, displayed hyperactivity, increased anxiety, and motor coordination impairments. Additionally, hippocampal-dependent learning and memory was affected, including working memory, long-term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, LoF produces autistic-like behaviors that are similar to human cases of ASD. These findings further support a role for dnLoF mutations in ASD and suggest +/- as a suitable model for ASD research.

SUMMARY STATEMENT

Autism spectrum disorder represents a growing patient population. Loss of one copy of the gene provides a promising mouse model that reproduces autistic-like behaviors for research and therapeutic testing.