{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:12:07Z","timestamp":1790107927273,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T00:00:00Z","timestamp":1424908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health Awards","award":["HD078678, MH57014, MH104158"],"award-info":[{"award-number":["HD078678, MH57014, MH104158"]}]},{"name":"Pitt-Hopkins Research Foundation (AJK and JDS) and Civitan International"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Pitt\u2013Hopkins syndrome (PTHS) is a neurodevelopmental disorder, classified as an autism spectrum disorder that is caused by the haploinsufficiency of Transcription Factor 4 (TCF4). The most common non\u2010neurological symptoms in PTHS patients are gastrointestinal (GI) disturbances, mainly gastroesophageal reflux and severe constipation (in about 30 and 75% of PTHS patients, respectively). We hypothesized that the recently recognized mouse model of PTHS will exhibit problems with their gut function. We conducted series of in vivo tests on 15\u2010 to 19\u2010 week old male mice, heterozygous for the <jats:italic>TCF4<\/jats:italic> functional deletion, mimicking the TCF4 haploinsufficiency in PTHS patients, and their wild type littermates. Data collection and initial analysis were performed blindly, that is, the genotyping key was received after the mean values were calculated for each individual animal, and then mean\/median of each group was subsequently calculated. Body weight, fecal pellet output, and fluid content were similar between the groups, indicating normal gross growth of PTHS mice and their overall physiological GI motility and intestinal secretion\/absorption. There were no significant differences in gut length and gross appearance pointing out that PTHS mice have normal gut in gross anatomical terms. However, the assessment of gut transit indicates that, while whole\u2010gut transit velocity was similar between the groups, the upper GI and distal colon transit velocities were significantly reduced in the PTHS mice. This is the first evidence of specific gut related problems in the PTHS mice. Our study also validates the <jats:italic>TCF4<\/jats:italic> functional knockout mice as an animal model to study PTHS\u2010associated GI disturbances. <jats:bold><jats:italic>Autism Res<\/jats:italic><\/jats:bold> <jats:italic>2015, 8: 629\u2013633<\/jats:italic>. \u00a9 2015 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/aur.1467","type":"journal-article","created":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T05:07:17Z","timestamp":1425013637000},"page":"629-633","source":"Crossref","is-referenced-by-count":39,"title":["Pitt\u2013Hopkins Mouse Model has Altered Particular Gastrointestinal Transits In Vivo"],"prefix":"10.1002","volume":"8","author":[{"given":"Vladimir","family":"Grubi\u0161i\u0107","sequence":"first","affiliation":[{"name":"Department of Neurobiology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Neurobiology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. David","family":"Sweatt","sequence":"additional","affiliation":[{"name":"Department of Neurobiology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Parpura","sequence":"additional","affiliation":[{"name":"Department of Neurobiology University of Alabama at Birmingham Birmingham Alabama"},{"name":"Department of Biotechnology University of Rijeka Rijeka Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/515582"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm099"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700913"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i44.5523"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707456104"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073169"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0160-09.2009"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604253341707"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.429-440.2000"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.061"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417028-5.00009-0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-006-1947-2"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","DOI":"10.4199\/C00010ED1V01Y201003DEB001","volume-title":"Transcriptional control of neural crest development","author":"Nelms B.L.","year":"2010"},{"key":"e_1_2_6_15_1","first-page":"182","article-title":"A syndrome of mental retardation, wide mouth and intermittent overbreathing","volume":"14","author":"Pitt D.","year":"1978","journal-title":"Australian Paediatric Journal"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39134"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.32"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06288-11"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21639"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.19.2.146"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14848"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.6.2898"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/515583"}],"container-title":["Autism Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Faur.1467","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Faur.1467","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aur.1467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:47:33Z","timestamp":1696625253000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/aur.1467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,26]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1002\/aur.1467"],"URL":"https:\/\/doi.org\/10.1002\/aur.1467","archive":["Portico"],"relation":{},"ISSN":["1939-3792","1939-3806"],"issn-type":[{"value":"1939-3792","type":"print"},{"value":"1939-3806","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,26]]}}}