{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:08Z","timestamp":1790524868422,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T00:00:00Z","timestamp":1531872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000852","name":"Henry Smith Charity","doi-asserted-by":"publisher","award":["NSCG1Q9R"],"award-info":[{"award-number":["NSCG1Q9R"]}],"id":[{"id":"10.13039\/501100000852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Tenascin\u2010X (TNX) is an extracellular matrix glycoprotein with anti\u2010adhesive properties in skin and joints. Here we report the novel finding that TNX is expressed in human and mouse gut tissue where it is exclusive to specific subpopulations of neurones.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our studies with TNX\u2010deficient mice show impaired defecation and neural control of distal colonic motility that can be rescued with a 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonist. However, colonic secretion is unchanged. They are also susceptible to internal rectal intussusception. Colonic afferent sensitivity is increased in TNX\u2010deficient mice. Correspondingly, there is increased density of and sensitivity of putative nociceptive fibres in TNX\u2010deficient mucosa.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A group of TNX\u2010deficient patients report symptoms highly consistent with those in the mouse model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings suggest TNX plays entirely different roles in gut to non\u2010visceral tissues \u2013 firstly a role in enteric motor neurones and secondly a role influencing nociceptive sensory neurones<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Studying further the mechanisms by which TNX influences neuronal function will lead to new targets for future treatment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The extracellular matrix (ECM) is not only an integral structural molecule, but is also critical for a wide range of cellular functions. The glycoprotein tenascin\u2010X (TNX) predominates in the ECM of tissues like skin and regulates tissue structure through anti\u2010adhesive interactions with collagen. Monogenic TNX deficiency causes painful joint hypermobility and skin hyperelasticity, symptoms characteristic of hypermobility Ehlers Danlos syndrome (hEDS). hEDS patients also report consistently increased visceral pain and gastrointestinal (GI) dysfunction. We investigated whether there is a direct link between TNX deficiency and GI pain or motor dysfunction. We set out first to learn where TNX is expressed in human and mouse, then determine how GI function, specifically in the colon, is disordered in TNX\u2010deficient mice and humans of either sex. In human and mouse tissue, TNX was predominantly associated with cholinergic colonic enteric neurones, which are involved in motor control. TNX was absent from extrinsic nociceptive peptidergic neurones. TNX\u2010deficient mice had internal rectal prolapse and a loss of distal colonic contractility which could be rescued by prokinetic drug treatment. TNX\u2010deficient patients reported increased sensory and motor GI symptoms including abdominal pain and constipation compared to controls. Despite absence of TNX from nociceptive colonic neurones, neuronal sprouting and hyper\u2010responsiveness to colonic distension was observed in the TNX\u2010deficient mice. We conclude that ECM molecules are not merely support structures but an integral part of the microenvironment particularly for specific populations of colonic motor neurones where TNX exerts functional influences.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276300","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T15:02:05Z","timestamp":1529420525000},"page":"4237-4251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["The extracellular matrix glycoprotein tenascin\u2010X regulates peripheral sensory and motor neurones"],"prefix":"10.1113","volume":"596","author":[{"given":"Rubina","family":"Aktar","sequence":"first","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madusha","family":"Peiris","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Fikree","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-0284","authenticated-orcid":false,"given":"Vincent","family":"Cibert\u2010Goton","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-4323","authenticated-orcid":false,"given":"Maxim","family":"Walmsley","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-9369","authenticated-orcid":false,"given":"Iain R.","family":"Tough","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology and Neuroscience Kings College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-233X","authenticated-orcid":false,"given":"Paulo","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"},{"name":"Department of Histology, Centre for Biological Sciences State University of Londrina  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo J. A.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"},{"name":"Department of Histology, Centre for Biological Sciences State University of Londrina  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar D.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marie","family":"Delalande","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-7877","authenticated-orcid":false,"given":"David C.","family":"Bulmer","sequence":"additional","affiliation":[{"name":"Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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