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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:p>\n                    Rett syndrome is an x-linked genetic neurological disorder primarily caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. This progressive neurodevelopmental condition hinders patients\u2019 ability to breathe and eat normally. It remains unclear how\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    deficiency leads to the high prevalence of dysphagia and aspiration pneumonia observed in individuals with Rett syndrome. This study aims to determine the effects of\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    deficiency on swallow-related neuromuscular mechanisms that contribute to dysphagia in Rett syndrome. Swallow-related submental complex duration and amplitude were significantly decreased in both\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    <jats:sup>\u2212\/y<\/jats:sup>\n                    and\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice compared to wild-type, likely due to reduced motor unit activation. In\n                    <jats:italic toggle=\"yes\">Mecp2-<\/jats:italic>\n                    deficient mice, cholinergic immunoreactivity in the hypoglossal, facial, and trigeminal motor nuclei was decreased in postsymptomatic, but not presymptomatic mice. We also observed a significant increase in the transition time from inspiration to swallow, swallow to the subsequent inspiration, and impaired post swallow respiratory rhythm resumption in\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    <jats:sup>\u2212\/y<\/jats:sup>\n                    , but not\n                    <jats:italic toggle=\"yes\">Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. The combination of decreased ChAT\n                    <jats:sup>+<\/jats:sup>\n                    cells in brainstem motor nuclei and reduced submental muscle complex activity suggest impaired swallow-related hyolaryngeal elevation and laryngeal vestibular closure. These results provide insight into a neuromuscular mechanism underlying dysphagia in Rett syndrome and support the use of\n                    <jats:italic toggle=\"yes\">Mecp2-<\/jats:italic>\n                    deficient mice as a viable preclinical model for further investigation of swallow and upper airway dysfunction in Rett syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2535716123","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:59:39Z","timestamp":1776355179000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Mecp2 deficiency induces dysphagia in a preclinical model of Rett syndrome"],"prefix":"10.1073","volume":"123","author":[{"given":"Luiz Marcelo","family":"Oliveira","sequence":"first","affiliation":[{"name":"Norcliffe Foundation Center for Integrative Brain Research, Seattle Children\u2019s Research Institute","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Saeed","family":"Aslam","sequence":"additional","affiliation":[{"name":"Norcliffe Foundation Center for Integrative Brain Research, Seattle Children\u2019s Research Institute","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Marino","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Norcliffe Foundation Center for Integrative Brain Research, Seattle Children\u2019s Research Institute","place":["Seattle"]},{"name":"Department of Neurological Surgery, University of Washington School of Medicine","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-251X","authenticated-orcid":false,"given":"Alyssa D.","family":"Huff","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, The George Washington University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1956.19.1.44"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00005.2021"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.929"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2013.09.006"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1044\/2019_PERS-SIG13-2018-0014"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00406.2002"},{"key":"e_1_3_4_7_2","first-page":"1","article-title":"Intrinsic fibre architecture and attachments of the human epiglottis and their contributions to the mechanism of deglutition","volume":"186","author":"Vandaele D.","year":"1995","unstructured":"D. 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