{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:42:59Z","timestamp":1782996179231,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","award":["W.OR17\u201013"],"award-info":[{"award-number":["W.OR17\u201013"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Muscle\u2010specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against MuSK in the neuromuscular junction (NMJ). MuSK MG patients have fluctuating, fatigable skeletal muscle weakness, in particular of bulbar muscles. Severity differs greatly between patients, in spite of comparable autoantibody levels. One explanation for inter\u2010patient and inter\u2010muscle variability in sensitivity might be variations in compensatory muscle responses. Previously, we developed a passive transfer mouse model for MuSK MG. In preliminary\n                    <jats:italic>ex vivo<\/jats:italic>\n                    experiments, we observed that muscle contraction of some mice, in particular those with milder myasthenia, had become partially insensitive to inhibition by \u03bc\u2010Conotoxin\u2010GIIIB, a blocker of skeletal muscle Na\n                    <jats:sub>V<\/jats:sub>\n                    1.4 voltage\u2010gated sodium channels. We hypothesised that changes in Na\n                    <jats:sub>V<\/jats:sub>\n                    channel expression profile, possibly co\u2010expression of (\u03bc\u2010Conotoxin\u2010GIIIB insensitive) Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5 type channels, might lower the muscle fibre's firing threshold and facilitate neuromuscular synaptic transmission. To test this hypothesis, we here performed passive transfer in immuno\u2010compromised mice, using \u2018high\u2019, \u2018intermediate\u2019 and \u2018low\u2019 dosing regimens of purified MuSK MG patient IgG4. We compared myasthenia levels, \u03bc\u2010Conotoxin\u2010GIIIB resistance and muscle fibre action potential characteristics and firing thresholds. High\u2010 and intermediate\u2010dosed mice showed clear, progressive myasthenia, not seen in low\u2010dosed animals. However, diaphragm NMJ electrophysiology demonstrated almost equal myasthenic severities amongst all regimens. Nonetheless, low\u2010dosed mouse diaphragms showed a much higher degree of \u03bc\u2010Conotoxin\u2010GIIIB resistance. This was not explained by upregulation of\n                    <jats:italic>Scn5a<\/jats:italic>\n                    (the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5 gene), lowered muscle fibre firing thresholds or histologically detectable upregulated Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5 channels. It remains to be established which factors are responsible for the observed \u03bc\u2010Conotoxin\u2010GIIIB insensitivity and whether the Na\n                    <jats:sub>V<\/jats:sub>\n                    repertoire change is compensatory beneficial or a bystander effect.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16347","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T01:07:40Z","timestamp":1713834460000},"page":"3292-3308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Change of voltage\u2010gated sodium channel repertoire in skeletal muscle of a MuSK myasthenia gravis mouse model"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-559X","authenticated-orcid":false,"given":"Olena","family":"Butenko","sequence":"first","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1568-5942","authenticated-orcid":false,"given":"Stine Marie","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne E.","family":"Filli\u00e9\u2010Grijpma","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2538-180X","authenticated-orcid":false,"given":"Robyn","family":"Verpalen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Verschuuren","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silv\u00e8re M.","family":"van der Maarel","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-5042","authenticated-orcid":false,"given":"Maartje G.","family":"Huijbers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-9090","authenticated-orcid":false,"given":"Jaap J.","family":"Plomp","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","first-page":"453","article-title":"The role of the diaphragm in lymphatic absorption from the peritoneal cavity","volume":"186","author":"Abu\u2010Hijleh M. F.","year":"1995","journal-title":"Journal of Anatomy"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08456.2001"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228225.23349.5d"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00707"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021014-071740"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81251-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168-3659(97)00238-1"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11272.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117302"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1248"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00357-4"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.03.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2015.12.016"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05438.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401281200"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws025"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00314"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00647-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2012.02.010"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.251827"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.01.013"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201611582"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8206.1"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2741\/4532"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2022.109551"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370513"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019429"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.04.018"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430315"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.04.038"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.04.004"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.1.180"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13249"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13543"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.01.025"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00199929"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6654"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.06.052"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.16347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T05:06:55Z","timestamp":1718341615000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.16347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/ejn.16347"],"URL":"https:\/\/doi.org\/10.1111\/ejn.16347","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.16347\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16347\/v2\/review2","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,22]]},"assertion":[{"value":"2023-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}