Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

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.

Background
音调拓扑（tonotopy）是听觉功能最核心的基本原则之一。尽管已有研究报道耳蜗的多种形态学与生理学特征存在梯度分布，但关于基因表达梯度模式的相关信息却极为匮乏。此外，常染色体显性非综合征性听力损失（autosomal dominant non-syndromic hearing loss）患者的听力图可呈现特征性表现，但其背后的致病机制尚未阐明。我们推测，耳蜗内基因表达的音调拓扑梯度或许正是这类特征性听力图的成因。

Methodology/Principal Findings
本研究采用微阵列技术与定量逆转录聚合酶链式反应（quantitative RT-PCR），对小鼠耳蜗顶圈、中圈与底圈的基因表达谱进行了比较分析。在检测的24547个基因中，共有783个已注释基因的表达量差异达2倍以上。本研究最显著的发现为：4个突变可引发常染色体显性耳聋的基因（Pou4f3、Slc17a8、Tmc1与Crym）的表达量呈现显著梯度分布，且此类基因在耳蜗顶圈的表达水平显著高于底圈。值得注意的是，可能对耳蜗功能具有关键调控作用的Emilin-2与Tectb基因，其表达量同样在顶圈高于底圈。

Conclusions/Significance
本研究为耳蜗内基因表达的梯度分布模式提供了基础数据。尤其针对那些突变可引发常染色体显性非综合征性听力损失的基因（Pou4f3、Slc17a8、Tmc1与Crym），以及对耳蜗功能至关重要的基因（Emilin-2与Tectb）而言，其表达量的梯度变化或可为阐释此类疾病的多样病理状态提供新的理论依据。