{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T20:48:20Z","timestamp":1772052500331,"version":"3.50.1"},"reference-count":46,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K21526"],"award-info":[{"award-number":["20K21526"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Government of Japan Ministry of Education Culture Sports Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020050","name":"Japan Intractable Diseases Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","cmghjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular and Molecular Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2023]]},"DOI":"10.1016\/j.jcmgh.2022.12.003","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T20:32:16Z","timestamp":1670877136000},"page":"1505-1524","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism"],"prefix":"10.1016","volume":"15","author":[{"given":"Mukhamad","family":"Sunardi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuya","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Uesaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-8885","authenticated-orcid":false,"given":"Hideki","family":"Enomoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jcmgh.2022.12.003_bib1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1177\/1093526619889434","article-title":"Are we underdiagnosing Hirschsprung disease?","volume":"23","author":"Kapur","year":"2020","journal-title":"Pediatr Devel Pathol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: signalling, biological functions and therapeutic value","volume":"3","author":"Airaksinen","year":"2002","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/367380a0","article-title":"Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret","volume":"367","author":"Schuchardt","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.2007.053959","article-title":"Hirschsprung disease, associated syndromes and genetics: a review","volume":"45","author":"Amiel","year":"2008","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/367377a0","article-title":"Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung\u2019s disease","volume":"367","author":"Romeo","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/367378a0","article-title":"Mutations of the RET proto-oncogene in Hirschsprung\u2019s disease","volume":"367","author":"Edery","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ng0595-35","article-title":"Loss of function effect of RET mutations causing Hirschsprung disease","volume":"10","author":"Pasini","year":"1995","journal-title":"Nat Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1053\/gast.2001.25515","article-title":"Functional analysis of RET with Hirschsprung mutations affecting its kinase domain","volume":"121","author":"Iwashita","year":"2001","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib9","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1136\/jmg.38.11.729","article-title":"Hirschsprung disease, associated syndromes, and genetics: a review","volume":"38","author":"Amiel","year":"2001","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib10","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrn2137","article-title":"Enteric nervous system development and Hirschsprung\u2019s disease: advances in genetic and stem cell studies","volume":"8","author":"Heanue","year":"2007","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/dgd.12664","article-title":"Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B- and Hirschsprung disease-associated missense mutations of the RET gene","volume":"62","author":"Nakatani","year":"2020","journal-title":"Development, Growth & Differentiation"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib12","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1073\/pnas.97.1.268","article-title":"A\u00a0human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus","volume":"97","author":"Bolk","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/(SICI)1098-1004(1997)9:3<243::AID-HUMU5>3.0.CO;2-8","article-title":"Frequency of RET mutations in long- and short-segment Hirschsprung disease","volume":"9","author":"Seri","year":"1997","journal-title":"Hum Mutat"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12882-016-0354-z","article-title":"Heterozygous p.S811F RET gene mutation associated with renal agenesis, oligomeganephronia and total colonic aganglionosis: a case report","volume":"17","author":"Sugimoto","year":"2016","journal-title":"BMC Nephrol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib15","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1523\/JNEUROSCI.5185-07.2008","article-title":"The neurotrophic effects of glial cell line-derived neurotrophic factor on spinal motoneurons are restricted to fusimotor subtypes","volume":"28","author":"Gould","year":"2008","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/dgd.12740","article-title":"Live visualization of a functional RET-EGFP chimeric receptor in homozygous knock-in mice","volume":"63","author":"Sunardi","year":"2021","journal-title":"Development, Growth & Differentiation"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib17","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.mod.2008.04.006","article-title":"Ret isoform function and marker gene expression in the enteric nervous system is conserved across diverse vertebrate species","volume":"125","author":"Heanue","year":"2008","journal-title":"Mech Dev"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib18","doi-asserted-by":"crossref","first-page":"8026","DOI":"10.1128\/MCB.24.18.8026-8036.2004","article-title":"A\u00a0targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia","volume":"24","author":"Jijiwa","year":"2004","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib19","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/nn.3184","article-title":"Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system","volume":"15","author":"Nishiyama","year":"2012","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib20","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1172\/JCI34425","article-title":"Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice","volume":"118","author":"Uesaka","year":"2008","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib21","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/ng998","article-title":"Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease","volume":"32","author":"Carrasquillo","year":"2002","journal-title":"Nat Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib22","first-page":"568","article-title":"A\u00a0genetic study of Hirschsprung disease","volume":"46","author":"Badner","year":"1990","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/1750-1172-8-184","article-title":"A\u00a0prospective observational study of associated anomalies in Hirschsprung\u2019s disease","volume":"8","author":"Pini Prato","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib24","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1093\/hmg\/ddz149","article-title":"A\u00a0gene regulatory network explains RET-EDNRB epistasis in Hirschsprung disease","volume":"28","author":"Chatterjee","year":"2019","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib25","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s100249900162","article-title":"Early death of neural crest cells is responsible for total enteric aganglionosis in Sox10(Dom)\/Sox10(Dom) mouse embryos","volume":"2","author":"Kapur","year":"1999","journal-title":"Pediatr Dev Pathol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib26","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1086\/338712","article-title":"Gdnf haploinsufficiency causes Hirschsprung-like intestinal obstruction and early-onset lethality in mice","volume":"70","author":"Shen","year":"2002","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005093","article-title":"Male-biased aganglionic megacolon in the TashT mouse line due to perturbation of silencer elements in a large gene desert of chromosome 10","volume":"11","author":"Bergeron","year":"2015","journal-title":"PLoS Genetics"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib28","first-page":"5423","article-title":"BMP4 knockdown of NCSCs leads to aganglionosis in the middle embryonic stage","volume":"17","author":"Li","year":"2018","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib29","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0534-20.2021","article-title":"Increased RET activity coupled with a reduction in the RET gene dosage causes intestinal aganglionosis in mice","volume":"8","author":"Okamoto","year":"2021","journal-title":"eNeuro"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib30","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1242\/dev.128.20.3963","article-title":"RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons","volume":"128","author":"Enomoto","year":"2001","journal-title":"Development"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib31","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1101\/gad.205001","article-title":"Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis","volume":"15","author":"de Graaff","year":"2001","journal-title":"Genes Dev"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib32","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.2353\/ajpath.2006.050607","article-title":"The Ret(C620R) mutation affects renal and enteric development in a mouse model of Hirschsprung\u2019s disease","volume":"168","author":"Carniti","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib33","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1242\/dev.02616","article-title":"Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells","volume":"133","author":"Asai","year":"2006","journal-title":"Development"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib34","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1172\/JCI41619","article-title":"Organotypic specificity of key RET adaptor-docking sites in the pathogenesis of neurocristopathies and renal malformations in mice","volume":"120","author":"Jain","year":"2010","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib35","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1242\/dev.01421","article-title":"Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret\u00a0in spermatogenesis","volume":"131","author":"Jain","year":"2004","journal-title":"Development"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib36","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1053\/j.gastro.2020.07.018","article-title":"Glial cell-derived neurotrophic factor induces enteric neurogenesis and improves colon structure and function in mouse models of Hirschsprung disease","volume":"159","author":"Soret","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib37","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1128\/MCB.18.6.3321","article-title":"Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism","volume":"18","author":"Cosma","year":"1998","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0092-8674(91)90616-7","article-title":"Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos","volume":"66","author":"Amaya","year":"1991","journal-title":"Cell"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib39","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1101\/gad.8.16.1897","article-title":"Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo","volume":"8","author":"Dumont","year":"1994","journal-title":"Genes Dev"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib40","doi-asserted-by":"crossref","first-page":"5799","DOI":"10.1073\/pnas.0510923103","article-title":"Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival","volume":"103","author":"Vajkoczy","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib41","article-title":"Electroporation enables the efficient mRNA delivery into the mouse zygotes and facilitates CRISPR\/Cas9-based genome editing","volume":"5","author":"Hashimoto","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib42","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0896-6273(00)80541-3","article-title":"GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys","volume":"21","author":"Enomoto","year":"1998","journal-title":"Neuron"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib43","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0896-6273(00)80541-3","article-title":"GFR a1-deficient mice have deficits in the enteric nervous system and kidneys","volume":"21","author":"Enomoto","year":"1998","journal-title":"Neuron"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib44","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.neuron.2004.10.032","article-title":"GFRalpha1 expression in cells lacking RET is dispensable for organogenesis and nerve regeneration","volume":"44","author":"Enomoto","year":"2004","journal-title":"Neuron"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib45","doi-asserted-by":"crossref","first-page":"G1266","DOI":"10.1152\/ajpgi.00444.2004","article-title":"Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice","volume":"288","author":"Kimball","year":"2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jcmgh.2022.12.003_bib46","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.expneurol.2009.04.023","article-title":"Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson\u2019s disease","volume":"218","author":"Greene","year":"2009","journal-title":"Exp Neurol"}],"container-title":["Cellular and Molecular Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352345X2200251X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352345X2200251X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:34:06Z","timestamp":1762454046000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352345X2200251X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023]]}},"alternative-id":["S2352345X2200251X"],"URL":"https:\/\/doi.org\/10.1016\/j.jcmgh.2022.12.003","relation":{},"ISSN":["2352-345X"],"issn-type":[{"value":"2352-345X","type":"print"}],"subject":[],"published":{"date-parts":[[2023]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism","name":"articletitle","label":"Article Title"},{"value":"Cellular and Molecular Gastroenterology and Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jcmgh.2022.12.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.","name":"copyright","label":"Copyright"}]}}