Progressive irreversible hearing loss is caused by stria vascularis degeneration in an Slc26a4-insufficient mouse model of large vestibular aqueduct syndrome. (3rd December 2015)

• Record Type: Journal Article
• Authors: Ito, T.; Nishio, A.; Wangemann, P.; Griffith, A.J.
• Is Part Of: Neuroscience. Volume 310(2015)
• Page Start: 188
• Page End: 197
• Publication Date: 2015-12-03
• Subjects: ABR auditory brainstem response -- DE17.5 doxycycline discontinued at embryonic day 17.5 -- E17.5 embryonic day 17.5 -- EP endocochlear potential -- EVA enlargement of the vestibular aqueduct -- PCR polymerase chain reaction -- SPL sound pressure level; deafness -- doxycycline -- fluctuation -- hypomorphic -- SLC26A4 -- stria vascularis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.09.016
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: SLC26A4 mutations can cause fluctuating and progressive hearing loss in humans. Slc26a4 -insufficient mice have irreversible hearing loss after 6 months of age. Stria vascularis degeneration underlies hearing loss in Slc26a4 -insufficient ears. Slc26a4 -insufficient mice may be used to study primary strial presbycusis. Abstract: Hearing loss of patients with enlargement of the vestibular aqueduct (EVA) can fluctuate or progress, with overall downward progression. The most common detectable cause of EVA is mutations of SLC26A4 . We previously described a transgenic Slc26a4 -insufficient mouse model of EVA in which Slc26a4 expression is controlled by doxycycline administration. Mice that received doxycycline from conception until embryonic day 17.5 (DE17.5; doxycycline discontinued at embryonic day 17.5) had fluctuating hearing loss between 1 and 6 months of age with an overall downward progression after 6 months of age. In this study, we characterized the cochlear functional and structural changes underlying irreversible hearing loss in DE17.5 mice at 12 months of age. The endocochlear potential was decreased and inversely correlated with auditory brainstem response thresholds. The stria vascularis was thickened and edematous in ears with less severe hearing loss, and thinned and atrophic in ears with more severe hearing loss. There were pathologic changes in marginal cell morphology and gene expression that were not observed at 3 months. We conclude that strial dysfunction and degeneration are the primary causes of irreversible progressive hearing loss in our Slc26a4 -insufficient mouse model of EVA. This model of primary strial atrophy may be used to explore the mechanisms of progressive hearing loss due to strial dysfunction.