{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:38:33Z","timestamp":1776087513058,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM063074"],"award-info":[{"award-number":["R01GM063074"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG\u20102001\u201036023"],"award-info":[{"award-number":["RG\u20102001\u201036023"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    encodes the contactin\u2010associated protein 1 (Cntnap1) which localizes to the paranodal region in all myelinated axons and is essential for axonal domain organization and the propagation of action potentials. To date, close to 45 reported human\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    variants have been identified that are associated with dysregulation and disorganization of the axonal domains, resulting in various forms of congenital hypomyelinating neuropathies in children. Currently, no treatments are available for neuropathies caused by\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    variants, highlighting the importance of fully characterizing these mutations and their impact on Cntnap1 functions. To understand the importance of a novel human\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    likely pathogenic variant that changes glycine at position 349 to valine in a child who also carries a\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    truncation and displayed severe neurological deficits, we used\n                    <jats:italic>CRISPR\/Cas9<\/jats:italic>\n                    methodology and introduced a single nucleotide substitution in the mouse\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    gene, resulting in glycine at 350 to valine (\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G350V<\/jats:italic>\n                    <\/jats:sup>\n                    ). Trans\u2010allelic combination of\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G350V<\/jats:italic>\n                    <\/jats:sup>\n                    with a\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    null allele (\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G350V\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mimics human pathologies, recapitulating hypomyelination neuropathies\n                    <jats:italic>associated with CNTNAP1<\/jats:italic>\n                    mutations as well as loss of paranodal junctions and disorganization of axonal domains in myelinated axons. Expression of the wild type\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    transgene in\n                    <jats:italic>Cntnap1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G350V\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice rescued the mutant phenotypes and restored all neurological deficits. Our studies demonstrate that GGT (glycine) to GTT (valine) change in human\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    creates a recessive loss of function allele and lays the foundation for potential gene therapy studies aimed at treating\n                    <jats:italic>CNTNAP1<\/jats:italic>\n                    \u2010associated hypomyelinating neuropathies in children.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70040","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T08:31:47Z","timestamp":1745397107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Mutation in\n                    <scp>\n                      <i>CNTNAP1<\/i>\n                    <\/scp>\n                    Gene Causes Disorganization of Axonal Domains, Hypomyelination and Severe Neurological Deficits"],"prefix":"10.1002","volume":"103","author":[{"given":"Lacey B.","family":"Sell","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carson","family":"Zabel","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine Weller","family":"Gr\u00f8nborg","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, Department of Pediatrics and Adolescent Medicine and Department of Genetics University Hospital Copenhagen Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-1498","authenticated-orcid":false,"given":"Manzoor A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.021"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.08.045"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(00)81126\u20105"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2003.09.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(01)00294\u2010x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06\u201006\u20100570"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309120200"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(01)00296\u20103"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23197"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113274"},{"key":"e_1_2_10_12_1","first-page":"97","article-title":"Sur une Forme Paticuliere d'Atrophie Musuculaire Progressive Souvent Familial, Debutante par les Pieds et les Jambes et Atteignant Plus Tard les Mains","volume":"6","author":"Charcot J. M.","year":"1886","journal-title":"Revue de M\u00e9decine Interne"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0960\u20109822(01)00680\u20107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007050\u20107"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl144"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073818776157"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.05.013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-05-01642.1998"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1006908013972"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100029(19980601)41:5<431::AID\u2010JEMT9>3.0.CO;2\u2010S"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1740925X06000275"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26658"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601082103"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2022.01.015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200309147"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270898"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102202\u201014\u201096"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010881\u2010y"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.09.007"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000144"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0558\u201020.2021"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3513"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.02.006"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt618"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.12.014"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135697"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100110\u2010x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25416"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(00)80942\u20103"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.480"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.30.051606.094309"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.142"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.5.978"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u20100839\u20109"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22015"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1253"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20\u201022\u201008354.2000"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22013"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8795607"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08602.x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08623.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24052"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0515\u201018.2018"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2661\u201016.2017"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(03)00628\u20107"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2024.102852"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.019"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2427\u201021.2022"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00201"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181be2e96"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.03.020"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0138\u201018.2018"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/400_2009_3"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.12.016"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5951\u201009.2010"},{"key":"e_1_2_10_67_1","unstructured":"Tooth H. H.1886.The Peroneal Type of Progressive Muscular AtrophyUniversity of Cambridge."},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.3.f97"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw093"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24650"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg151"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn511374\u201020201021\u201000739"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200712154"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:08:05Z","timestamp":1754906885000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.70040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/jnr.70040"],"URL":"https:\/\/doi.org\/10.1002\/jnr.70040","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.70040\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70040\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70040\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70040\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70040\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70040\/v1\/review1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70040"}}