{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:07:09Z","timestamp":1780654029399,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005969","name":"Universit\u00e0 di Bologna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15171"],"award-info":[{"award-number":["GGP15171"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004740","name":"Fondazione del Monte di Bologna e Ravenna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004740","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK084567"],"award-info":[{"award-number":["P30DK084567"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK57061"],"award-info":[{"award-number":["R01DK57061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK106011"],"award-info":[{"award-number":["R01DK106011"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>RAD21 is a double\u2010strand\u2010break repair protein and component of the cohesin complex with key roles in cellular functions. A RAD21 loss\u2010of\u2010function mutation was found in cases of chronic intestinal pseudo\u2010obstruction (CIPO) with associated enteric neuronal loss. Analysis of RAD21 expression in the enteric nervous system is lacking, thus we aimed to characterize RAD21 immunoreactivity (IR) in myenteric ganglia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Double labeling immunofluorescence in mouse and human jejunum was used to determine colocalization of RAD21 with HuC\/D, PGP9.5, neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), choline acetyl transferase (ChAT), Kit, platelet\u2010derived growth factor receptor\u2010\u03b1 (PDGFR\u03b1), and glial fibrillary acid protein (GFAP) IRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A subset of PGP9.5\u2010 and HuC\/D\u2010IR neuronal cell bodies and nerve fibers in the myenteric plexus of human and mouse small intestine also displayed cytoplasmic RAD21\u2010IR Cytoplasmic RAD21\u2010IR was found in 43% of HuC\/D\u2010IR neurons in adult and neonatal mice but did not colocalize with nNOS. A subset of ChAT\u2010positive neurons had cytoplasmic RAD21\u2010IR Punctate RAD21\u2010IR was restricted to the nucleus in most cell types consistent with labeling of the cohesin complex. Cytoplasmic RAD21\u2010IR was not detected in interstitial cells of Cajal, fibroblast\u2010like cells or glia. Subsets of neurons in primary culture exhibited cytoplasmic RAD21\u2010IR Suppression of RAD21 expression by shRNA knockdown abolished RAD21\u2010IR in cultured neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data showing cytoplasmic RAD21 expression in enteric neurons provide a basis toward understanding how mutations of this gene may contribute to altered neuronal function\/survival thus leading to gut\u2010motor abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13429","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T13:03:06Z","timestamp":1533301386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expression of RAD21 immunoreactivity in myenteric neurons of the human and mouse small intestine"],"prefix":"10.1111","volume":"30","author":[{"given":"F.","family":"Bianco","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna Bologna Italy"},{"name":"Department of Veterinary Medical Sciences (DIMEVET) University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. T.","family":"Eisenman","sequence":"additional","affiliation":[{"name":"Enteric NeuroScience Program Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Colmenares Aguilar","sequence":"additional","affiliation":[{"name":"Enteric NeuroScience Program Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bonora","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Clavenzani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences (DIMEVET) University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-0387","authenticated-orcid":false,"given":"D. R.","family":"Linden","sequence":"additional","affiliation":[{"name":"Enteric NeuroScience Program Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-5873","authenticated-orcid":false,"given":"R.","family":"De Giorgio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Nuovo Arcispedale S.Anna University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Farrugia","sequence":"additional","affiliation":[{"name":"Enteric NeuroScience Program Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-5993","authenticated-orcid":false,"given":"S. J.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Enteric NeuroScience Program Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"13","article-title":"Enhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers","volume":"21","author":"Xu H","year":"2011","journal-title":"Breast Cancer Res"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2007.01093.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.136507.111"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006389"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.12.034"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12945"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13127"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201844"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.08.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.85"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2006.05.003"},{"issue":"2","key":"e_1_2_10_13_1","first-page":"30","article-title":"Distribution of RAD21 immunoreactivity in mouse and human gut neurons","volume":"29","author":"Bianco F","year":"2017","journal-title":"Neurogastroenterol Motil"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01245.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.06.017"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/90.3.497"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061376"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00472.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151323"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.23.8267-8277.2002"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti281"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619406114"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012112"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.046"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.13429","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T01:14:59Z","timestamp":1694999699000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":23,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/nmo.13429"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13429","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"2018-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13429"}}