{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:05Z","timestamp":1785413645538,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,14]]},"group-title":"Genetics","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/04mvr1r74","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CDG-UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Phosphomannomutase 2 (PMM2) deficiency is the most common congenital disorders of glycosylation (CDG) with an estimated incidence ranging from 1:20,000 to 1:80,000. Patients manifest a broad spectrum of clinical manifestations, with neurological deficits often emerging as the earliest sign, and may progress to severe multi-organ dysfunction. Mortality reaches 20% by the age of six, primarily due to severe infections, liver insufficiency, or cardiomyopathy. The pathophysiology of the tissue-specific complications remains unclear and there is currently no cure for the disease. In this study, we performed omics analyses of cerebella isolated from a mouse model of PMM2-CDG. RNA-Seq analysis revealed altered gene expression in pathways involved in immune responses and coagulation, while proteomic analysis of proteins enriched by lectin-affinity chromatography identified proteins required for neurodevelopment and neurotransmission. We validated our results by demonstrating significant downregulation of Neurexin-2 in the\n                  <jats:italic>Pmm2<\/jats:italic>\n                  knockout (KO) mouse cerebella and showed that its reduced abundance can be reversed by AAV9-\n                  <jats:italic>PMM2<\/jats:italic>\n                  gene treatment of the\n                  <jats:italic>Pmm2<\/jats:italic>\n                  KO mice.\n                <\/jats:p>","DOI":"10.1101\/2025.08.11.669733","type":"posted-content","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T04:05:14Z","timestamp":1755230714000},"source":"Crossref","is-referenced-by-count":0,"title":["AAV-based gene replacement reverses Neurexin-2 downregulation in the cerebellum of a mouse model of phosphomannomutase 2 deficiency (PMM2-CDG)"],"prefix":"10.64898","author":[{"given":"M","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025081804500986000_2025.08.11.669733v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-59565-2.00044-7"},{"key":"2025081804500986000_2025.08.11.669733v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0129-4"},{"key":"2025081804500986000_2025.08.11.669733v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cww086"},{"key":"2025081804500986000_2025.08.11.669733v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072092"},{"key":"2025081804500986000_2025.08.11.669733v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-88"},{"key":"2025081804500986000_2025.08.11.669733v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200470"},{"key":"2025081804500986000_2025.08.11.669733v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.719437"},{"key":"2025081804500986000_2025.08.11.669733v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200011)16:5<386::AID-HUMU2>3.0.CO;2-Y"},{"key":"2025081804500986000_2025.08.11.669733v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.06.021"},{"key":"2025081804500986000_2025.08.11.669733v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12024"},{"key":"2025081804500986000_2025.08.11.669733v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109052"},{"key":"2025081804500986000_2025.08.11.669733v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12826"},{"key":"2025081804500986000_2025.08.11.669733v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.11.003"},{"key":"2025081804500986000_2025.08.11.669733v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109188"},{"key":"2025081804500986000_2025.08.11.669733v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-025-00525-w"},{"key":"2025081804500986000_2025.08.11.669733v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.01.657261"},{"key":"2025081804500986000_2025.08.11.669733v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167163"},{"key":"2025081804500986000_2025.08.11.669733v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114976"},{"key":"2025081804500986000_2025.08.11.669733v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113883"},{"key":"2025081804500986000_2025.08.11.669733v1.20","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.07.663468"},{"key":"2025081804500986000_2025.08.11.669733v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12110"},{"key":"2025081804500986000_2025.08.11.669733v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025081804500986000_2025.08.11.669733v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.027"},{"key":"2025081804500986000_2025.08.11.669733v1.24","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104903"},{"key":"2025081804500986000_2025.08.11.669733v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-00415-7"},{"key":"2025081804500986000_2025.08.11.669733v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90306-2"},{"key":"2025081804500986000_2025.08.11.669733v1.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403244111"},{"key":"2025081804500986000_2025.08.11.669733v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-9-213"},{"key":"2025081804500986000_2025.08.11.669733v1.29","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.210091"},{"key":"2025081804500986000_2025.08.11.669733v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nature07456"},{"key":"2025081804500986000_2025.08.11.669733v1.31","doi-asserted-by":"publisher","DOI":"10.3390\/cells14120911"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.11.669733","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:20:50Z","timestamp":1768468850000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.11.669733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":31,"URL":"https:\/\/doi.org\/10.1101\/2025.08.11.669733","relation":{},"subject":[],"published":{"date-parts":[[2025,8,14]]},"subtype":"preprint"}}