Limits...
Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice.

Li X, Xu L, Li J, Li B, Bai X, Strauss JF, Zhang Z, Wang H - PLoS ONE (2014)

Bottom Line: These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating.However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction.Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes.

View Article: PubMed Central - PubMed

Affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, Shandong Province, PR China.

ABSTRACT
Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes.

Show MeSH

Related in: MedlinePlus

Analyses of cilia in the epithelial cells of the middle ear and Eustachian tubes.(A) Normal-looking cilia in the middle ear epithelial cells of 25-day old wild-type mice, the cilia were well organized. (B) Cilia in the middle ear epithelial cells of 25-day old Spag6-deficient mice, notice that the cilia were largely disordered. Cilia were present in the promontorium tympani of 25-day old wild-type mice (C), but were prematurely lost in the Spag6-deficient mice (D). WT, wild-type; M, mutant; Bars: A, 10 µm; B, 15 µm; C and D, 25 µm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231073&req=5

pone-0112879-g003: Analyses of cilia in the epithelial cells of the middle ear and Eustachian tubes.(A) Normal-looking cilia in the middle ear epithelial cells of 25-day old wild-type mice, the cilia were well organized. (B) Cilia in the middle ear epithelial cells of 25-day old Spag6-deficient mice, notice that the cilia were largely disordered. Cilia were present in the promontorium tympani of 25-day old wild-type mice (C), but were prematurely lost in the Spag6-deficient mice (D). WT, wild-type; M, mutant; Bars: A, 10 µm; B, 15 µm; C and D, 25 µm.

Mentions: SEM result showed that cilia of the wild-type mice (at P25) were well-organized in the middle ear epithelial cells (Figure 3A). However, there was significant reduction in cilia density of the Spag6-deficient mice (at P25), and the cilia were largely arrayed in a disordered fashion (Figure 3B). Cilia were present in the promontorium tympani of the wild-type mice (Figure 3C), but, they prematurely disappeared in the Spag6-deficient mice (Figure 3D).


Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice.

Li X, Xu L, Li J, Li B, Bai X, Strauss JF, Zhang Z, Wang H - PLoS ONE (2014)

Analyses of cilia in the epithelial cells of the middle ear and Eustachian tubes.(A) Normal-looking cilia in the middle ear epithelial cells of 25-day old wild-type mice, the cilia were well organized. (B) Cilia in the middle ear epithelial cells of 25-day old Spag6-deficient mice, notice that the cilia were largely disordered. Cilia were present in the promontorium tympani of 25-day old wild-type mice (C), but were prematurely lost in the Spag6-deficient mice (D). WT, wild-type; M, mutant; Bars: A, 10 µm; B, 15 µm; C and D, 25 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231073&req=5

pone-0112879-g003: Analyses of cilia in the epithelial cells of the middle ear and Eustachian tubes.(A) Normal-looking cilia in the middle ear epithelial cells of 25-day old wild-type mice, the cilia were well organized. (B) Cilia in the middle ear epithelial cells of 25-day old Spag6-deficient mice, notice that the cilia were largely disordered. Cilia were present in the promontorium tympani of 25-day old wild-type mice (C), but were prematurely lost in the Spag6-deficient mice (D). WT, wild-type; M, mutant; Bars: A, 10 µm; B, 15 µm; C and D, 25 µm.
Mentions: SEM result showed that cilia of the wild-type mice (at P25) were well-organized in the middle ear epithelial cells (Figure 3A). However, there was significant reduction in cilia density of the Spag6-deficient mice (at P25), and the cilia were largely arrayed in a disordered fashion (Figure 3B). Cilia were present in the promontorium tympani of the wild-type mice (Figure 3C), but, they prematurely disappeared in the Spag6-deficient mice (Figure 3D).

Bottom Line: These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating.However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction.Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes.

View Article: PubMed Central - PubMed

Affiliation: Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, Shandong Province, PR China.

ABSTRACT
Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes.

Show MeSH
Related in: MedlinePlus