{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:07Z","timestamp":1785435787692,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,29]]},"group-title":"Neuroscience","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS146406"],"award-info":[{"award-number":["R01NS146406"]}]},{"name":"NIH","award":["R03MH127401"],"award-info":[{"award-number":["R03MH127401"]}]},{"name":"NIH","award":["R01DC019380"],"award-info":[{"award-number":["R01DC019380"]}]},{"name":"NIH","award":["R35GM156374"],"award-info":[{"award-number":["R35GM156374"]}]},{"award":["Provost's Undergraduate Research Award (PURA)"],"award-info":[{"award-number":["Provost's Undergraduate Research Award (PURA)"]}],"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Lloyd B. Minor Center for Vestibular and Skull Base Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Autism spectrum disorder (ASD) is frequently accompanied by sensory and motor abnormalities, including impaired balance, postural control, and spatial orientation, that are often attributed largely to altered central circuitry. Emerging evidence, however, suggests that peripheral sensory dysfunction can also shape ASD related behavioral phenotypes. Here, we tested whether loss of the ASD associated gene\n                  <jats:italic>Cntnap2<\/jats:italic>\n                  \/Caspr2 alters vestibular signaling in\n                  <jats:italic>\n                    Cntnap2\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice. Developmental transcriptomic analysis showed that\n                  <jats:italic>Cntnap2<\/jats:italic>\n                  is expressed in vestibular sensory organs and increases during the first postnatal month, coincident with vestibular pathway maturation. Vestibular sensory evoked potentials revealed reduced response amplitudes and prolonged latencies in\n                  <jats:italic>Cntnap2<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice, indicating impaired peripheral afferent responses to transient linear acceleration.\n                  <jats:italic>\n                    Cntnap2\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice also showed delayed contact righting, reduced ocular counter roll, and increased hindlimb slips and compensatory tail excursions during balance beam walking, whereas rotational vestibulo-ocular reflex gain and phase were preserved. These vestibular and balance abnormalities were accompanied by reduced novel arm preference in the Y maze and severe impairment of Barnes maze acquisition, consistent with impaired spatial learning. Together, these findings identify\n                  <jats:italic>Cntnap2<\/jats:italic>\n                  \/Caspr2 as a regulator of vestibular sensory signaling and support a model in which disrupted peripheral vestibular input, likely acting together with central effects of\n                  <jats:italic>Cntnap2<\/jats:italic>\n                  loss, contributes to sensorimotor and spatial cognitive phenotypes relevant to ASD.\n                <\/jats:p>","DOI":"10.64898\/2026.05.28.728446","type":"posted-content","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:55:23Z","timestamp":1780066523000},"source":"Crossref","is-referenced-by-count":0,"title":["Autism associated\n                  <i>Cntnap2<\/i>\n                  deletion disrupts vestibular sensory signaling and spatial cognition in mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7607-766X","authenticated-orcid":false,"given":"Yvette","family":"Shu","sequence":"first","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"},{"name":"Department of Molecular and Cellular Biology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9993-3377","authenticated-orcid":false,"given":"Yushan","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9554-5006","authenticated-orcid":false,"given":"Dyllan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Deng","sequence":"additional","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-2324","authenticated-orcid":false,"given":"Liliana D.","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4646-2388","authenticated-orcid":false,"given":"Tara","family":"Deemyad","sequence":"additional","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroush G.","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Center for Hearing and Balance, Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060112350632000_2026.05.28.728446v1.1","first-page":"7568572","article-title":"Balance and Vestibular Deficits in Pediatric Patients with Autism Spectrum Disorder: An Underappreciated Clinical Aspect","volume":"2022","year":"2022","journal-title":"Autism Res Treat"},{"key":"2026060112350632000_2026.05.28.728446v1.2","doi-asserted-by":"crossref","unstructured":"Mansour Y , Burchell A , Kulesza RJ . Central Auditory and Vestibular Dysfunction Are Key Features of Autism Spectrum Disorder. Front Integr Neurosci. 2021;15.","DOI":"10.3389\/fnint.2021.743561"},{"key":"2026060112350632000_2026.05.28.728446v1.3","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1007\/s10803-019-04059-0","article-title":"Vestibular Function in Children with Neurodevelopmental Disorders: A Systematic Review","volume":"49","year":"2019","journal-title":"J Autism Dev Disord"},{"key":"2026060112350632000_2026.05.28.728446v1.4","doi-asserted-by":"crossref","unstructured":"Seif A , Guerville R , Rajab M , Marceau-Linhares C , Schaaf K , Schmid S , et al. 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