Barbara R Grubb

UNCCH, School of Medicine, Medicine

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Inactivation of Chibby affects function of motile airway cilia

Vera A. Voronina; Ken-Ichi Takemaru; Piper Treuting; Damon Love; Barbara R. Grubb; Adeline M. Hajjar; Allison Adams; Feng-Qian Li; Randall T. Moon (Profiled Author: Barbara R Grubb)

Journal of Cell Biology. 2009;185(2):225-233.

Chibby (Cby) is a conserved component of the Wntβ-catenin pathway. Cby physically interacts with β-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. © 2009 Voronina et al.

PMID: 19364920     PMCID: PMC2700371

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