Inactivation of Chibby affects function of motile airway cilia.
Chibby (Cby) is a conserved component of the Wnt-beta-catenin pathway. Cby physically interacts with beta-catenin to repress its activation of transcription. To elucidate the function of Cby in vertebrates, we generated Cby(-/-) mice and found that after 2-3 d of weight loss, the majority of mice die before or around weaning. All Cby(-/-) mice develop rhinitis and sinusitis. When challenged with Pseudomonas aeruginosa isolates, Cby(-/-) mice are unable to clear the bacteria from the nasal cavity. Notably, Cby(-/-) mice exhibit a complete absence of mucociliary transport caused by a marked paucity of motile cilia in the nasal epithelium. Moreover, ultrastructural experiments reveal impaired basal body docking to the apical surface of multiciliated cells. In support of these phenotypes, endogenous Cby protein is localized at the base of cilia. As the phenotypes of Cby(-/-) mice bear striking similarities to primary ciliary dyskinesia, Cby(-/-) mice may prove to be a useful model for this condition.
Voronina
Vera A
VA
Department of Pharmacology, Howard Hughes Medical Institute, USA.
Takemaru
Ken-Ichi
K
Treuting
Piper
P
Love
Damon
D
Grubb
Barbara R
BR
Hajjar
Adeline M
AM
Adams
Allison
A
Li
Feng-Qian
FQ
Moon
Randall T
RT
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D002925:Ciliary Motility Disorders / Q000235:genetics; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009079:Mucociliary Clearance / Q000502:physiology*; D009297:Nasal Mucosa / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010033:Otitis Media / Q000235:genetics; D010641:Phenotype; D012220:Rhinitis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D012852:Sinusitis / Q000235:genetics; D015996:Survival Rate; D014018:Tissue Distribution; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D002352:Carrier Proteins; C517894:Chibby protein, mouse; D009687:Nuclear Proteins; D051153:Wnt Proteins; D051176:beta Catenin