{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:54:41Z","timestamp":1768510481651,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,18]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,18]]},"abstract":"<jats:p>\n                  Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. We recently reported a family with a paternally inherited intragenic\n                  <jats:italic>ASTN2<\/jats:italic>\n                  duplication with a range of neurodevelopmental disorders, including autism spectrum disorder (ASD), learning difficulties, and speech and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional\n                  <jats:italic>Astn2<\/jats:italic>\n                  knockout (KO and cKO, respectively) mouse lines.\n                  <jats:italic>Astn2<\/jats:italic>\n                  KO mice exhibit strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity and repetitive behaviors, altered social behaviors, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors were also prominent in\n                  <jats:italic>Astn2<\/jats:italic>\n                  cKO animals. By Golgi staining,\n                  <jats:italic>Astn2<\/jats:italic>\n                  KO PCs have region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of\n                  <jats:italic>Astn2<\/jats:italic>\n                  KO cerebellum reveals a marked upregulation of ASTN2 family member, ASTN1, a neuron-glial adhesion protein. Immunohistochemistry and electron microscopy demonstrate a large increase in Bergmann glia volume in the molecular layer of\n                  <jats:italic>Astn2<\/jats:italic>\n                  KO animals. Electrophysiological experiments indicate a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents (IPSCs) in the\n                  <jats:italic>Astn2<\/jats:italic>\n                  KO animals, suggesting that pre- and postsynaptic components of synaptic transmission are altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.\n                <\/jats:p>","DOI":"10.1101\/2024.02.18.580354","type":"posted-content","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T04:11:21Z","timestamp":1708315881000},"source":"Crossref","is-referenced-by-count":2,"title":["Mice lacking\n                  <i>Astn2<\/i>\n                  have ASD-like behaviors and altered cerebellar circuit properties"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5777-2405","authenticated-orcid":false,"given":"Michalina","family":"Hanzel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-4937","authenticated-orcid":false,"given":"Kayla","family":"Fernando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5585-4722","authenticated-orcid":false,"given":"Susan E","family":"Maloney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shioaching","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-5614","authenticated-orcid":false,"given":"K\u00e4rt","family":"M\u00e4tlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-3530","authenticated-orcid":false,"given":"H Amalia","family":"Pasolli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Heissel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph D","family":"Dougherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0360-8367","authenticated-orcid":false,"given":"Court","family":"Hull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-660X","authenticated-orcid":false,"given":"Mary E","family":"Hatten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.02.18.580354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:58:33Z","timestamp":1768456713000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.02.18.580354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,18]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2024.02.18.580354","relation":{},"subject":[],"published":{"date-parts":[[2024,2,18]]},"subtype":"preprint"}}