ArticlePloS one2015
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Genome-wide DNA methylation analysis of human peripheral blood reveals susceptibility loci of diabetes-related hearing loss.Journal of human genetics · 2018Trial
- RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond.Scientific reports · 2025Article
- Epigenetic Modifications in Sensorineural Hearing Loss: Protective Mechanisms and Therapeutic Potential.Current medical science · 2025Review
- Complete omission of exon 21 from Slc12a2 transcripts in mice results in hearing loss.Scientific reports · 2025Article
- Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea.Scientific reports · 2024Article
- Review
- Refined Auditory Brainstem Response Measurement Identified Potential Models of Congenital Deafness in Laboratory Mouse Strains.JMA journal · 2019Article
- Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse.Scientific reports · 2016Article
- Gene expression profiling of DBA/2J mice cochleae treated with l-methionine and valproic acid.Genomics data · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: <smallcaps>L</smallcaps>-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of <smallcaps>L</smallcaps>-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.
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