{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:31:15Z","timestamp":1792186275963,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)\u2013left\u2013right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP\u2013left\u2013right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.<\/jats:p>","DOI":"10.1165\/rcmb.2015-0353oc","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T20:21:22Z","timestamp":1456345282000},"page":"213-224","source":"Crossref","is-referenced-by-count":134,"title":["DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes"],"prefix":"10.1093","volume":"55","author":[{"given":"Gerard W.","family":"Dougherty","sequence":"first","affiliation":[{"name":"Department of General Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki T.","family":"Loges","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Klinkenbusch","sequence":"additional","affiliation":[{"name":"Department 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A.","family":"Kashef","sequence":"additional","affiliation":[{"name":"Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"},{"name":"Baystate Medical Center, Springfield, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kashef","sequence":"additional","affiliation":[{"name":"Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fardin","family":"Eghtedari","sequence":"additional","affiliation":[{"name":"Australian Capital Territory Health, Canberra, Australian Capital Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"H\u00e4ffner","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, University of Freiburg, Freiburg, 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