Ryan C. Neff, Katherine A. Stangis, Ujjawal Beniwal, Ty Hergenreder, Bing Ye, Geoffrey G. Murphy
{"title":"Cognitive behavioral phenotyping of DSCAM heterozygosity as a model for autism spectrum disorder","authors":"Ryan C. Neff, Katherine A. Stangis, Ujjawal Beniwal, Ty Hergenreder, Bing Ye, Geoffrey G. Murphy","doi":"10.1111/gbb.70002","DOIUrl":null,"url":null,"abstract":"<p>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 de novo loss-of-function (dnLoF) mutations in the <i>Down Syndrome Cell Adhesion Molecule (DSCAM)</i> as a strong risk factor for ASD. Previous research has shown that <i>DSCAM</i> ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent <i>DSCAM</i> 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 <i>DSCAM</i>, as in the <i>DSCAM</i><sup>2J</sup>+/−, that is, <i>DSCAM</i> heterozygous mice, displayed hyperactivity, increased anxiety-like behavior, and motor coordination deficits. Additionally, hippocampal-dependent learning and memory was affected, including impairments in working memory, long-term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, <i>DSCAM</i> LoF produces autistic-like behaviors that are similar to those observed in human cases of ASD. These findings further support a role for <i>DSCAM</i> dnLoF mutations in ASD and suggest <i>DSCAM</i><sup>2J</sup>+/− as a suitable model for ASD research.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70002","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes Brain and Behavior","FirstCategoryId":"102","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gbb.70002","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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 de novo loss-of-function (dnLoF) mutations in the Down Syndrome Cell Adhesion Molecule (DSCAM) as a strong risk factor for ASD. Previous research has shown that DSCAM ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent DSCAM 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 DSCAM, as in the DSCAM2J+/−, that is, DSCAM heterozygous mice, displayed hyperactivity, increased anxiety-like behavior, and motor coordination deficits. Additionally, hippocampal-dependent learning and memory was affected, including impairments in working memory, long-term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, DSCAM LoF produces autistic-like behaviors that are similar to those observed in human cases of ASD. These findings further support a role for DSCAM dnLoF mutations in ASD and suggest DSCAM2J+/− as a suitable model for ASD research.
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