Journal
NATURE GENETICS
Volume 46, Issue 6, Pages 646-651Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.2961
Keywords
-
Categories
Funding
- Dubai Harvard Foundation for Medical Research Collaborative Research Grant
- Generallacility Grant from the Health Science Center, Kuwait University [SRUL02/13]
- Deutsche Forschungsgemeinschaft (DFG) [Om 6/4]
- Interdisziplinaeres Zentrum fiir Kfinische Forschung (IZKF) [Om2/009/12]
- European Community's Seventh Framework Programme FP7/2009 [241955]
- SYSCILIA
- BESTCILIA [305404]
- [GM096021]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available