{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:18:27Z","timestamp":1790443107233,"version":"4.1.0"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"name":"Children\u2019s Discovery Institute of Washington University and St. Louis Children\u2019s Hospital","award":["MD-II2013-269"],"award-info":[{"award-number":["MD-II2013-269"]}]},{"name":"NIH grant RO1","award":["DK087715"],"award-info":[{"award-number":["DK087715"]}]},{"DOI":"10.13039\/100000912","name":"March of Dimes","doi-asserted-by":"crossref","award":["6-FY15-235"],"award-info":[{"award-number":["6-FY15-235"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Burroughs Wellcome Fund Clinical Scientist Award in Translational Research","award":["1008525"],"award-info":[{"award-number":["1008525"]}]},{"name":"National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award","award":["UL1TR001108"],"award-info":[{"award-number":["UL1TR001108"]}]},{"name":"Irma and Norman Braman Endowment","award":["Endowment funding"],"award-info":[{"award-number":["Endowment funding"]}]},{"name":"Suzi and Scott Lustgarten Center Endowment","award":["Endowment Funding"],"award-info":[{"award-number":["Endowment Funding"]}]},{"name":"Indiana Clinical and Translational Sciences 656 Institute","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,6]]},"abstract":"<jats:p>\n                    Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung disease (HSCR), a developmental defect in which the enteric nervous system (ENS) is missing from the distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Postsurgical problems, such as enterocolitis and soiling, are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in 2 DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including\n                    <jats:italic>Dscam<\/jats:italic>\n                    and\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    , which are hypothesized to contribute to HSCR risk. Ts65Dn and Tc1 mice have normal ENS precursor migration at E12.5 and almost normal myenteric plexus structure as adults. However, Ts65Dn and Tc1 mice have markedly reduced submucosal plexus neuron density throughout the bowel. Surprisingly, the submucosal neuron defect in Ts65Dn mice is not due to excess\n                    <jats:italic>Dscam<\/jats:italic>\n                    or\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    , since normalizing copy number for these genes does not rescue the defect. These findings suggest the possibility that the high frequency of bowel problems in children with DS and HSCR may occur because of additional unrecognized problems with ENS structure.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.124510","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T11:53:16Z","timestamp":1555674796000},"source":"Crossref","is-referenced-by-count":12,"title":["Down syndrome mouse models have an abnormal enteric nervous system"],"prefix":"10.1172","volume":"4","author":[{"given":"Ellen M.","family":"Schill","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA."},{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Abramson Research Center, Philadelphia, Pennsylvania, 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