Audiology and Neurotology

Original Paper

Progressive Hearing Loss in Mice with a Mutated Vitamin D Receptor Gene

Zou J.a · Minasyan A.b · Keisala T.b · Zhang Y.a · Wang J.-H.b · Lou Y.-R.b · Kalueff A.b · Pyykkö I.a · Tuohimaa P.b, c

Author affiliations

Departments of aOtolaryngology, and bAnatomy, School of Medicine, University of Tampere, cDepartment of Clinical Chemistry, Tampere University Hospital, Tampere, Finland

Keywords: CalciumGanglion cellHearing lossVitamin DCaspase

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Audiol Neurotol 2008;13:219–230
https://doi.org/10.1159/000115431

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 13, 2007
Accepted: October 19, 2007
Published online: February 07, 2008
Issue release date: June 2008

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 1

ISSN: 1420-3030 (Print)
eISSN: 1421-9700 (Online)

For additional information: https://www.karger.com/AUD

Abstract

Background: Both hypo- and hypervitaminosis D can cause sensorineural hearing loss, and aural symptoms due to vitamin D insufficiency are especially common during gravidity. Hormonal forms of vitamin D regulate transcription by binding with the high-affinity vitamin D receptor (VDR). Objective: To assess the effects of impaired vitamin D action in VDR knockout (KO) mice on hearing, cochlear morphology, and cochlear gene expression. Materials and Methods: Eighteen young male and female mice (10 VDR KO and 8 wild type, WT, ≤6 months old), 33 adult male and female mice (16 VDR KO and 17 WT, between 7 and 14 months old), and 11 aged male and female mice (5 VDR KO and 6 WT, ≧15 months old) on 129S1 genetic background were studied. Auditory thresholds were evaluated by auditory brain stem response. Morphological changes were analyzed using plastic embedding and light microscopy. The expression of key genes (known to play a role in the regulation of cochlear function), and caspase 3 activity, were assessed using immunofluorescent confocal microscopy. Results: There was a statistically significant difference between the young and the adult groups, and between the adult and aged groups of WT mice. There was also a statistically significant difference between the adult and aged groups in VDR KO mice, and between the young WT group and the young VDR KO group. Spiral ganglion cell loss was observed in the basal turn of adult VDR KO mice, a phenomenon infrequently found in WT mice. Expression of connexin 26, KCNJ10, and transient receptor potential channel vanilloid subfamily 4/6 was not affected by VDR KO-mediated hearing loss. Caspase 3 activation was detected in the spiral ganglion cell and its satellite cells, stria vascularis, spiral ligament fibrocytes, and the organ of Corti in both genotypes. However, the percentage of positive cells and the staining intensity were lower in the VDR KO (compared to the WT) mice. Conclusion: These data suggest that sensorineural hearing loss progressively developed at an earlier age in VDR KO mice. While the fundamental gene expressions in the cochlea were not influenced by VDR mutation, it resulted in decrease of caspase 3 activation, which may be one of the factors underlying accelerating age-related hearing loss observed in VDR KO mice.

© 2008 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 13, 2007
Accepted: October 19, 2007
Published online: February 07, 2008
Issue release date: June 2008

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 1

ISSN: 1420-3030 (Print)
eISSN: 1421-9700 (Online)

For additional information: https://www.karger.com/AUD

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2008, Vol.13, No. 4

June 2008

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