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

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.

Figure 1. Microscopical image of the mouse cochlea (right ear).

Bars indicate the incision points for each turn sample. A: apical turn, B: middle turn, C: basal turn, D: dissection example

Figure 2. Scatter plot analysis of gene expression profile of each cochlear turn.

Black lines indicate equal gene expression and red lines indicate 2-fold gene expression. A: apical turn vs. basal turn, B: apical turn vs. middle turn, C: middle turn vs. basal turn.

Figure 3. Gene expression patterns found by microarray analysis and quantitative RT-PCR.

Values of each gene expression are indicated as a relative value to the basal turn. The expression level of each gene measured by microarray analysis (solid lines) was comparable with the level measured by quantitative RT-PCR (dotted lines).