Deafness gene expression patterns in the mouse cochlea found by microarray analysis

PLoS One. 2014 Mar 27;9(3):e92547. doi: 10.1371/journal.pone.0092547. eCollection 2014.

Abstract

Background: Tonotopy is one of the most fundamental principles of auditory function. While gradients in various morphological and physiological characteristics of the cochlea have been reported, little information is available on gradient patterns of gene expression. In addition, the audiograms in autosomal dominant non syndromic hearing loss can be distinctive, however, the mechanism that accounts for that has not been clarified. We thought that it is possible that tonotopic gradients of gene expression within the cochlea account for the distinct audiograms.

Methodology/principal findings: We compared expression profiles of genes in the cochlea between the apical, middle, and basal turns of the mouse cochlea by microarray technology and quantitative RT-PCR. Of 24,547 genes, 783 annotated genes expressed more than 2-fold. The most remarkable finding was a gradient of gene expression changes in four genes (Pou4f3, Slc17a8, Tmc1, and Crym) whose mutations cause autosomal dominant deafness. Expression of these genes was greater in the apex than in the base. Interestingly, expression of the Emilin-2 and Tectb genes, which may have crucial roles in the cochlea, was also greater in the apex than in the base.

Conclusions/significance: This study provides baseline data of gradient gene expression in the cochlea. Especially for genes whose mutations cause autosomal dominant non syndromic hearing loss (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear function (Emilin-2 and Tectb), gradual expression changes may help to explain the various pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Cochlea / metabolism*
  • Computational Biology
  • Deafness / genetics*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Potassium Channels / genetics
  • Reproducibility of Results
  • Sodium Channels / genetics
  • Transcriptome*
  • mu-Crystallins

Substances

  • Calcium Channels
  • Crym protein, mouse
  • Potassium Channels
  • Sodium Channels
  • mu-Crystallins

Grants and funding

This study was supported by a Health and Labour Sciences Research Grant for Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare of Japan (S.U.), and by a Grant-in-Aid for Scientific Research from the (then) Ministry of Education, Science and Culture of Japan (http://www.mext.go.jp/english/) (S.U., Y.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.