{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:45:31Z","timestamp":1788561931267,"version":"build-2803163510"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sophia Foundation","award":["SSWO 17-18"],"award-info":[{"award-number":["SSWO 17-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Filamin A (FLNA) is a cytoplasmic actin binding protein, recently shown to be expressed as a long and short isoform. Mutations in FLNA are associated with a wide spectrum of disorders, including an X-linked form of chronic intestinal pseudo-obstruction (CIPO). However, the role of FLNA in intestinal development and function is largely unknown. In this study, we show that FLNA is expressed in the muscle layer of the small intestine from early human fetal stages. Expression of FLNA variants associated with CIPO, blocked expression of the long flna isoform and led to an overall reduction of RNA and protein levels. As a consequence, contractility of human intestinal smooth muscle cells was affected. Lastly, our transgenic zebrafish line showed that the flna long isoform is required for intestinal elongation and peristalsis. Histological analysis revealed structural and architectural changes in the intestinal smooth muscle of homozygous fish, likely triggered by the abnormal expression of intestinal smooth muscle markers. No defect in the localization or numbers of enteric neurons was observed. Taken together, our study demonstrates that the long FLNA isoform contributes to intestinal development and function. Since loss of the long FLNA isoform does not seem to affect the enteric nervous system, it likely results in a myopathic form of CIPO, bringing new insights to disease pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddac199","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T17:58:54Z","timestamp":1660845534000},"page":"151-160","source":"Crossref","is-referenced-by-count":16,"title":["The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction"],"prefix":"10.1093","volume":"32","author":[{"given":"Almira","family":"Zada","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"},{"name":"Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi 710004 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Halim","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Windster","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"},{"name":"Department of Pediatric Surgery, Erasmus University Medical Center Rotterdam, Sophia Children's Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herma C","family":"van der Linde","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackleen","family":"Glodener","sequence":"additional","affiliation":[{"name":"Department of Biology , Rollins Research Center, , Atlanta, GA 30322 , USA"},{"name":"Emory University , Rollins Research Center, , Atlanta, GA 30322 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Overkleeft","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca M","family":"de Graaf","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M","family":"Verdijk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus University Medical Center , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice S","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department of Biology , Rollins Research Center, , Atlanta, GA 30322 , USA"},{"name":"Emory University , Rollins Research Center, , Atlanta, GA 30322 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi 710004 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"},{"name":"Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M W","family":"Hofstra","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"},{"name":"Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0083-5318","authenticated-orcid":false,"given":"Maria M","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Sophia Children\u2019s Hospital , Rotterdam 3015GD , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"key":"2023011312215362300_ref1","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1007\/s11064-008-9684-y","article-title":"Filamin A mutant lacking actin-binding domain restores mu opioid receptor regulation in melanoma cells","volume":"33","author":"Onoprishvili","year":"2008","journal-title":"Neurochem. Res."},{"key":"2023011312215362300_ref2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4161\/cam.5.2.14401","article-title":"The filamins: organizers of cell structure and function","volume":"5","author":"Nakamura","year":"2011","journal-title":"Cell Adhes. Migr."},{"key":"2023011312215362300_ref3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.gde.2005.04.001","article-title":"Filamin A: phenotypic diversity","volume":"15","author":"Robertson","year":"2005","journal-title":"Curr. Opin. Genet. Dev."},{"key":"2023011312215362300_ref4","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/humu.24002","article-title":"The X-linked filaminopathies: synergistic insights from clinical and molecular analysis","volume":"41","author":"Wade","year":"2020","journal-title":"Hum. 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