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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia
Nature Genetics, Volume 46, No. 6, Year 2014
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Description
Using a whole-exome sequencing strategy, we identified recessive CCNO (encoding cyclin O) mutations in 16 individuals suffering from chronic destructive lung disease due to insufficient airway clearance. Respiratory epithelial cells showed a marked reduction in the number of multiple motile cilia (MMC) covering the cell surface. The few residual cilia that correctly expressed axonemal motor proteins were motile and did not exhibit obvious beating defects. Careful subcellular analyses as well as in vitro ciliogenesis experiments in CCNO-mutant cells showed defective mother centriole generation and placement. Morpholino-based knockdown of the Xenopus ortholog of CCNO also resulted in reduced MMC and centriole numbers in embryonic epidermal cells. CCNO is expressed in the apical cytoplasm of multiciliated cells and acts downstream of multicilin, which governs the generation of multiciliated cells. To our knowledge, CCNO is the first reported gene linking an inherited human disease to reduced MMC generation due to a defect in centriole amplification and migration. © 2014 Nature America, Inc.
Authors & Co-Authors
Wallmeier, Julia
Germany, Munster
Universitätsklinikum Münster
Al-Mutairi, Dalal A.
Kuwait, Kuwait City
Kuwait University
Chen, Chun Ting
United States, San Diego
Salk Institute for Biological Studies
Loges, Niki Tomas
Germany, Munster
Universitätsklinikum Münster
Pennekamp, Petra
Germany, Munster
Universitätsklinikum Münster
Menchen, Tabea
Germany, Munster
Universitätsklinikum Münster
Ma, Lina
United States, San Diego
Salk Institute for Biological Studies
Shamseldin, Hanan E.
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Olbrich, Heike
Germany, Munster
Universitätsklinikum Münster
Dougherty, Gerard W.
Germany, Munster
Universitätsklinikum Münster
Werner, Claudius
Germany, Munster
Universitätsklinikum Münster
Alsabah, Basel H.
Kuwait, Kuwait City
Zain Hospital
Köhler, Gabriele
Germany, Munster
Universitätsklinikum Münster
Jaspers, Martine
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Boon, Mieke
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Griese, Matthias
Germany, Munich
Klinikum Der Universität München
Schmitt-Grohé, Sabina
Germany, Bonn
Universitätsklinikum Bonn
Zimmermann, Theodor
Germany, Erlangen
Universitätsklinikum Erlangen
Koerner-Rettberg, Cordula
Germany, Bochum
St. Josef-hospital Im Katholischen Klinikum Bochum
Horak, Elisabeth
Austria, Innsbruck
Medizinische Universitat Innsbruck
Kintner, Chris
United States, San Diego
Salk Institute for Biological Studies
Alkuraya., Fowzan S.
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Saudi Arabia, Riyadh
College of Medicine Alfaisal University
Omran, Heymut
Germany, Munster
Universitätsklinikum Münster
Statistics
Citations: 226
Authors: 23
Affiliations: 12
Identifiers
Doi:
10.1038/ng.2961
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Genetics And Genomics