{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:05:58Z","timestamp":1768511158119,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,3]]},"group-title":"Neuroscience","reference-count":63,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>de novo<\/jats:italic>\n                  loss-of-function (dnLoF) mutations in the\n                  <jats:italic>Down Syndrome Cell Adhesion Molecule (DSCAM)<\/jats:italic>\n                  as a strong risk factor for ASD. Previous research has shown that\n                  <jats:italic>DSCAM<\/jats:italic>\n                  ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent\n                  <jats:italic>DSCAM<\/jats:italic>\n                  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\n                  <jats:italic>DSCAM<\/jats:italic>\n                  , as in the\n                  <jats:italic>DSCAM<\/jats:italic>\n                  <jats:sup>2J<\/jats:sup>\n                  +\/\u2212 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,\n                  <jats:italic>DSCAM<\/jats:italic>\n                  LoF produces autistic-like behaviors that are similar to human cases of ASD. These findings further support a role for\n                  <jats:italic>DSCAM<\/jats:italic>\n                  dnLoF mutations in ASD and suggest\n                  <jats:italic>DSCAM<\/jats:italic>\n                  <jats:sup>2J<\/jats:sup>\n                  +\/\u2212 as a suitable model for ASD research.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary Statement<\/jats:title>\n                  <jats:p>\n                    Autism spectrum disorder represents a growing patient population. Loss of one copy of the\n                    <jats:italic>DSCAM<\/jats:italic>\n                    gene provides a promising mouse model that reproduces autistic-like behaviors for research and therapeutic testing.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.06.03.597158","type":"posted-content","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T15:35:21Z","timestamp":1717428921000},"source":"Crossref","is-referenced-by-count":1,"title":["Cognitive behavioral phenotyping of\n                  <i>DSCAM<\/i>\n                  heterozygosity as a model for autism spectrum disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6913-7561","authenticated-orcid":false,"given":"Ryan C.","family":"Neff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6071-0366","authenticated-orcid":false,"given":"Katherine A.","family":"Stangis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ujjawal","family":"Beniwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ty","family":"Hergenreder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-4065","authenticated-orcid":false,"given":"Bing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3691-1722","authenticated-orcid":false,"given":"Geoffrey G.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024060513451092000_2024.06.03.597158v1.1","doi-asserted-by":"crossref","unstructured":"Agron, A. 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