{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:28:57Z","timestamp":1768076937933,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,10,17]],"date-time":"2012-10-17T00:00:00Z","timestamp":1350432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Autoimmune gastrointestinal dysmotility (AGID) is a limited form of dysautonomia. The only proven effector to date is IgG specific for ganglionic nicotinic\u2010acetylcholine receptors containing \u03b13 subunits [\u03b13*\u2010 nicotinic acetylcholine receptor (nAChR)]. Rabbits immunized with recombinant \u03b13\u2010polypeptide produce \u03b13*\u2010nAChR autoantibodies, and profound AGID ensues. Human and rabbit \u03b13*\u2010nAChR\u2010specific\u2010IgGs induce transient hypomotility when injected into mice. Here, we describe success and problems encountered inducing gastrointestinal hypomotility in mice by active immunization.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> We repeatedly injected young adult mice of seven different strains susceptible to autoimmunity (spontaneous diabetes or neural antigen immunization\u2010induced myasthenia gravis or encephalomyelitis) with: (i) \u03b13\u2010polypeptide, intradermally or (ii) live \u03b13*\u2010nAChR\u2010expressing xenogeneic cells, intraperitoneally. We measured serum \u03b13*\u2010nAChR\u2010IgG twice monthly, and terminally assessed blue dye gastrointestinal transit, total small intestinal \u03b13*\u2010nAChR content (radiochemically) and myenteric plexus neuron numbers (immunohistochemically, ileal\u2013jejunal whole\u2010mount preparations).<\/jats:p><jats:p><jats:bold>Key Results\u2002<\/jats:bold> Standard cutaneous inoculation with \u03b13\u2010polypeptide was minimally immunogenic, regardless of dose. Intraperitoneally injected live cells were potently immunogenic. Self\u2010reactive \u03b13*\u2010nAChR\u2010IgG was induced only by rodent immunogen; small intestinal transit slowing and enteric \u03b13*\u2010nAChR loss required high serum levels. Ganglionic neurons were not lost.<\/jats:p><jats:p><jats:bold>Conclusions &amp; Inferences\u2002<\/jats:bold> Autoimmune gastrointestinal dysmotility is inducible in mice by active immunization. Accompanying enteric \u03b13*\u2010nAChR reduction without neuronal death is consistent with an IgG\u2010mediated rather than T cell\u2010mediated pathogenesis, as is improvement of symptoms in patients receiving antibody\u2010depleting therapies.<\/jats:p>","DOI":"10.1111\/nmo.12030","type":"journal-article","created":{"date-parts":[[2012,10,17]],"date-time":"2012-10-17T11:26:11Z","timestamp":1350473171000},"page":"84","source":"Crossref","is-referenced-by-count":15,"title":["Gastrointestinal hypomotility with loss of enteric nicotinic acetylcholine receptors: active immunization model in mice"],"prefix":"10.1111","volume":"25","author":[{"given":"J. W.","family":"Meeusen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. E.","family":"Haselkorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. P.","family":"Fryer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. J.","family":"Kryzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. J.","family":"Gibbons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. A.","family":"Lennon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,10,17]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90593-A"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009213431204"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.06.018"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(20010201)49:2<146::AID-ANA34>3.0.CO;2-E"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.04.009"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901213400311"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a92b52"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0838-9"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1485-04.2004"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17429"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.2.322"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.78"},{"key":"e_1_2_9_14_2","first-page":"1013","volume-title":"Manual of Clinical and Laboratory Immunology","author":"Vernino S","year":"2002"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.11.005"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1981.tb33737.x"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1501s77"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002040210"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1806"},{"key":"e_1_2_9_20_2","first-page":"77","volume-title":"Cholinergic Mechanisms and Psychopharmacology: Advances in Behavioral Biology","author":"Lennon VA","year":"1977"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109980108"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000263185.30294.61"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051719"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.12030","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.12030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T03:20:31Z","timestamp":1698636031000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.12030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,17]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1111\/nmo.12030"],"URL":"https:\/\/doi.org\/10.1111\/nmo.12030","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,17]]}}}