{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:52:46Z","timestamp":1780455166183,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">CHARGE<\/jats:styled-content>syndrome is linked to autosomal\u2010dominant mutations in the<jats:italic><jats:styled-content style=\"fixed-case\">CHD<\/jats:styled-content>7<\/jats:italic>gene and results in a number of physiological and structural abnormalities, including heart defects, hearing and vision loss, and gastrointestinal (<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>) problems. Of these challenges,<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>problems have a profound impact throughout an individual's life, resulting in increased morbidity and mortality. A homolog of<jats:italic><jats:styled-content style=\"fixed-case\">CHD<\/jats:styled-content>7<\/jats:italic>has been identified in the zebrafish, the loss of which recapitulates many of the features of the human disease. Using a morpholino<jats:italic>chd7<\/jats:italic>knockdown model complemented by a<jats:italic>chd7<\/jats:italic>null mutant zebrafish line, we examined<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>structure, innervation, and motility in larval zebrafish. Loss of<jats:italic>chd7<\/jats:italic>resulted in physically smaller<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>tracts with normal epithelial and muscular histology, but decreased and disorganized vagal projections, particularly in the foregut.<jats:italic>chd7<\/jats:italic>morphant larvae had significantly less ability to empty their<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>tract of gavaged fluorescent beads, and this condition was only minimally improved by the prokinetic agents, domperidone and erythromycin, in keeping with mixed responses to these agents in patients with<jats:styled-content style=\"fixed-case\">CHARGE<\/jats:styled-content>syndrome. The conserved genetics and transparency of the zebrafish have provided new insights into the consequences of<jats:italic>chd7<\/jats:italic>gene dysfunction on the<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>system and cranial nerve patterning. These findings highlight the opportunity of the zebrafish to serve as a preclinical model for studying compounds that may improve<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>motility in individuals with<jats:styled-content style=\"fixed-case\">CHARGE<\/jats:styled-content>syndrome.<\/jats:p>","DOI":"10.1111\/febs.14473","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T23:34:10Z","timestamp":1523921650000},"page":"2125-2140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Etiology and functional validation of gastrointestinal motility dysfunction in a zebrafish model of<scp>CHARGE<\/scp>syndrome"],"prefix":"10.1111","volume":"285","author":[{"given":"Kellie","family":"Cloney","sequence":"first","affiliation":[{"name":"Faculty of Medicine Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby L.","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Stoyek","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger P.","family":"Croll","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medical Neuroscience Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey V.","family":"Prykhozhij","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Obstetrics and Gynaecology Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Midgen","sequence":"additional","affiliation":[{"name":"Department of Pathology Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Blake","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Dalhousie University Halifax Canada"},{"name":"Department of Pediatrics Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason N.","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dalhousie University Halifax Canada"},{"name":"Department of Pathology Dalhousie University Halifax Canada"},{"name":"Department of Microbiology and Immunology Dalhousie University Halifax Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30560"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201778"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80454-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992289803700302"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30559"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32179"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-007-9111-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1407"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-1-34"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087106"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.05.002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.07.026"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01260"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.07.013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031650"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.026765"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12306"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-004-0026-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.13012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2016.01.009"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1095-8649.2003.00149.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21705"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw198"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002642"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0022-3565(25)23692-8","article-title":"Dopamine regulation of [3H] acetylcholine release from guinea\u2010pig stomach","volume":"234","author":"Kusonoki M","year":"1985","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.07.004"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20075"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199004123221502"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl537"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.163"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2007.05.016"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38458"},{"key":"e_1_2_8_34_1","volume-title":"The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio)","author":"Westerfield M","year":"2007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.11.002"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098186"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308335110"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dss023"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23764"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00330.2016"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.042"},{"key":"e_1_2_8_42_1","first-page":"e4434","article-title":"Microgavage of zebrafish larvae","volume":"72","author":"Cocchiaro JL","year":"2013","journal-title":"J Vis Exp"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2012.10.003"},{"key":"e_1_2_8_44_1","volume-title":"Categorical Data Analysis","author":"Agresti AA","year":"2013"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxp050"},{"key":"e_1_2_8_46_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2013"},{"key":"e_1_2_8_47_1","volume-title":"RStudio: Integrated Development for R","author":"R Core Team","year":"2015"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.14473","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14473","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.14473","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T18:28:10Z","timestamp":1751567290000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.14473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/febs.14473"],"URL":"https:\/\/doi.org\/10.1111\/febs.14473","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,27]]},"assertion":[{"value":"2017-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}