English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Pendred syndrome, an autosomal-recessive disorder characterized by deafness and goiter, is caused by a mutation of  SLC26A4 , which codes for the anion exchanger pendrin. We investigated the relationship between pendrin expression and deafness using mice that have ( Slc26a4  +/+  or  Slc26a4  +/- ) or lack ( Slc26a4  -/- ) a complete  Slc26a4  gene. Previously, we reported that stria vascularis of adult  Slc26a4  -/-  mice is hyperpigmented and that marginal cells appear disorganized. Here we determine the time course of hyperpigmentation and marginal cell disorganization, and test the hypothesis that inflammation contributes to this tissue degeneration.    Methods   Slc26a4  -/-  and age-matched control ( Slc26a4  +/+  or  Slc26a4  +/- ) mice were studied at four postnatal (P) developmental stages: before and after the age that marks the onset of hearing (P10 and P15, respectively), after weaning (P28-41) and adult (P74-170). Degeneration and hyperpigmentation stria vascularis was evaluated by confocal microscopy. Gene expression in stria vascularis was analyzed by microarray and quantitative RT-PCR. In addition, the expression of a select group of genes was quantified in spiral ligament, spleen and liver to evaluate whether expression changes seen in stria vascularis are specific for stria vascularis or systemic in nature.    Results  Degeneration of stria vascularis defined as hyperpigmentation and marginal cells disorganization was not seen at P10 or P15, but occurred after weaning and was associated with staining for  CD68 , a marker for macrophages. Marginal cells in  Slc26a4  -/- , however, had a larger apical surface area at P10 and P15. No difference in the expression of  Lyzs ,  C3  and  Cd45  was found in stria vascularis of P15  Slc26a4  +/-  and  Slc26a4  -/-  mice. However, differences in expression were found after weaning and in adult mice. No difference in the expression of markers for acute inflammation, including  Il1a ,  Il6 ,  Il12a ,  Nos2  and  Nos3  were found at P15, after weaning or in adults. The expression of macrophage markers including  Ptprc  (=  Cd45 ),  Cd68 ,  Cd83 ,  Lyzs ,  Lgals3  (=  Mac2  antigen),  Msr2 , Cathepsins B, S, and K ( Ctsb, Ctss, Ctsk ) and complement components  C1r ,  C3  and  C4  was significantly increased in stria vascularis of adult  Slc26a4  -/-  mice compared to  Slc26a4  +/+  mice. Expression of macrophage markers  Cd45  and  Cd84  and complement components  C1r  and  C3  was increased in stria vascularis but not in spiral ligament, liver or spleen of  Slc26a4  -/-  compared to  Slc26a4  +/-  mice. The expression of  Lyzs  was increased in stria vascularis and spiral ligament but not in liver or spleen.    Conclusion  The data demonstrate that hyperpigmentation of stria vascularis and marginal cell reorganization in  Slc26a4  -/-  mice occur after weaning, coinciding with an invasion of macrophages. The data suggest that macrophage invasion contributes to tissue degeneration in stria vascularis, and that macrophage invasion is restricted to stria vascularis and is not systemic in nature. The delayed onset of degeneration of stria vascularis suggests that a window of opportunity exists to restore/preserve hearing in mice and therefore possibly in humans suffering from Pendred syndrome.

Macrophage invasion contributes to degeneration of stria vascularis in Pendred syndrome mouse model