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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.

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Normal Eustachian tube angle in Spag6-deficient mice.(A) The panel showed a direct view of a dissected skull with the lines of reference for the measured angles indicated. (B) The panel showed a graphic comparison of the mean values for angles L and R between mutant (n = 8) and wild-type (n = 8) mice. There is no significant difference in Eustachian tube angles between the wild-type and the mutant mice (Student t test, P>0.05). Error bars indicate the SEM.
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pone-0112879-g008: Normal Eustachian tube angle in Spag6-deficient mice.(A) The panel showed a direct view of a dissected skull with the lines of reference for the measured angles indicated. (B) The panel showed a graphic comparison of the mean values for angles L and R between mutant (n = 8) and wild-type (n = 8) mice. There is no significant difference in Eustachian tube angles between the wild-type and the mutant mice (Student t test, P>0.05). Error bars indicate the SEM.

Mentions: Eustachian tube abnormalities are often related to the increased OM incidence. Thus, Eustachian tube angles were measured between Spag6-deficient mice and their wild-type littermates to determine whether Eustachian tube angle contributes to OM in mutant mice. There was no significant difference between the mutant mice and the wild-type mice, indicating normal Eustachian tube angle in the mutants (Figure 8).


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)

Normal Eustachian tube angle in Spag6-deficient mice.(A) The panel showed a direct view of a dissected skull with the lines of reference for the measured angles indicated. (B) The panel showed a graphic comparison of the mean values for angles L and R between mutant (n = 8) and wild-type (n = 8) mice. There is no significant difference in Eustachian tube angles between the wild-type and the mutant mice (Student t test, P>0.05). Error bars indicate the SEM.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112879-g008: Normal Eustachian tube angle in Spag6-deficient mice.(A) The panel showed a direct view of a dissected skull with the lines of reference for the measured angles indicated. (B) The panel showed a graphic comparison of the mean values for angles L and R between mutant (n = 8) and wild-type (n = 8) mice. There is no significant difference in Eustachian tube angles between the wild-type and the mutant mice (Student t test, P>0.05). Error bars indicate the SEM.
Mentions: Eustachian tube abnormalities are often related to the increased OM incidence. Thus, Eustachian tube angles were measured between Spag6-deficient mice and their wild-type littermates to determine whether Eustachian tube angle contributes to OM in mutant mice. There was no significant difference between the mutant mice and the wild-type mice, indicating normal Eustachian tube angle in the mutants (Figure 8).

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