{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:15:20Z","timestamp":1791411320322,"version":"4.3.3"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"44","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 380\/15-1"],"award-info":[{"award-number":["RA 380\/15-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FR 1725\/5-1"],"award-info":[{"award-number":["FR 1725\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10,29]]},"abstract":"<jats:p>\n                    Gastrointestinal dysfunctions in individuals with autism spectrum disorder are poorly understood, although they are common among this group of patients.\n                    <jats:italic>FOXP1<\/jats:italic>\n                    haploinsufficiency is characterized by autistic behavior, language impairment, and intellectual disability, but feeding difficulties and gastrointestinal problems have also been reported. Whether these are primary impairments, the result of altered eating behavior, or side effects of psychotropic medication remains unclear. To address this question, we investigated\n                    <jats:italic>Foxp1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice reflecting\n                    <jats:italic>FOXP1<\/jats:italic>\n                    haploinsufficiency. These animals show decreased body weight and altered feeding behavior with reduced food and water intake. A pronounced muscular atrophy was detected in the esophagus and colon, caused by reduced muscle cell proliferation. Nitric oxide-induced relaxation of the lower esophageal sphincter was impaired and achalasia was confirmed in vivo by manometry. Foxp1 targets (\n                    <jats:italic>Nexn<\/jats:italic>\n                    ,\n                    <jats:italic>Rbms3<\/jats:italic>\n                    , and\n                    <jats:italic>Wls<\/jats:italic>\n                    ) identified in the brain were dysregulated in the adult\n                    <jats:italic>Foxp1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    esophagus. Total gastrointestinal transit was significantly prolonged due to impaired colonic contractility. Our results have uncovered a previously unknown dysfunction (achalasia and impaired gut motility) that explains the gastrointestinal disturbances in patients with FOXP1 syndrome, with potential wider relevance for autism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1911429116","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T20:55:37Z","timestamp":1571086537000},"page":"22237-22245","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":51,"title":["Gastrointestinal dysfunction in autism displayed by altered motility and achalasia in\n                    <i>Foxp1<\/i>\n                    <sup>+\/\u2212<\/sup>\n                    mice"],"prefix":"10.1073","volume":"116","author":[{"given":"Henning","family":"Fr\u00f6hlich","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Luise","family":"Kollmeyer","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie Catherine","family":"Linz","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Stuhlinger","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Groneberg","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of W\u00fcrzburg, D-97070 W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Reigl","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of W\u00fcrzburg, D-97070 W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Zizer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Ulm, D-89081 Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Friebe","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of W\u00fcrzburg, D-97070 W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Niesler","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"},{"name":"Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Rappold","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, D-69120 Heidelberg, Germany;"},{"name":"Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,10,14]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1854"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21362"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104579"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-017-0172-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.116"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.267989.115"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1005-17.2017"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127671"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.305037.117"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01287"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.01003.x"},{"key":"e_1_3_4_12_2","unstructured":"H. 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