DPOAE PHENOTYPING OF COCHLEAR FUNCTION

这项计划中的研究旨在开发一种根据小鼠外周耳朵的功能状态对其进行表型鉴定的快速方法。第1-1.5年的初步实验集中于开发一种使用失真产物耳声发射(DPOAEs)的方案，该方案适用于筛查大量小鼠的耳蜗病。为了实现这一目标，2f1-f2 DPOAE将以DPgram的形式在三个级别上获得，该DPOAEs将在从5.6到48.5 kHz(f2=60 kHz)的几何平均值的范围内以每八度10点的频率范围进行测试。这些措施将从代表40个独特品系的小鼠的双耳记录下来，每个品系n=12只小鼠。此外，这种DPOAE筛查数据将在同一小鼠的两个年龄段获得，即2个月龄和5个月龄。通过这些数据创建的数据库将被分析，以确定正常CBA类型小鼠的DPOAE水平的第5个百分位数，以及耳蜗功能受损的小鼠(如C57)的第95个百分位数。百分位数数据将被用来设计一个标准化图表，在该图表上可以绘制正在进行突变的单个小鼠的数据，以确定耳蜗功能是正常的还是受损的。与这些实验相关联的是，将与一家领先的听觉研究设备制造商一起开发一种商业仪器，可以在市场上提供，这样科学界就可以获得确定未知小鼠耳蜗功能状态的能力。该项目的第二阶段将在研究的第1.5至3年的另一组小鼠身上进行，目的是根据这40个小鼠品系对噪音导致听力损失的敏感性，为它们建立一个类似的数据库。为了实现这一目标，在获得基线DP图后，在3mo时，小鼠将暴露于标准八度频带噪声中，该噪声可导致DPOAE水平的永久性下降，然后在2周后重新测试，以记录噪声过度暴露对耳蜗功能的影响。这些暴露的小鼠群体中的百分位数将构成另一个标准化图表的基础，用于确定单个小鼠对声音过度刺激的敏感度。这两个项目将共同确立DPOAE测试的有用性，目的是开发简单而快速的筛查方法来确定单个小鼠的耳蜗功能状态。所产生的数据将以数据库和相关培训手册的形式在互联网上广泛提供。

The planned studies are designed to develop a rapid means of phenotyping mice according to the functional status of their peripheral ears. The initial experiments in Years 1-1.5 focus on developing a protocol using distortion-product otoacoustic emissions (DPOAEs) that is suitable for screening large numbers of mice for cochlear abnormalities. Toward this goal, 2f1-f2 DPOAEs will be obtained at three levels in the form of DPgrams that will test at 10 points per octave over a frequency extent that ranges from a geometric mean of 5.6 to 48.5 kHz (f2=60 kHz). These measures will be recorded from both ears of mice representing 40 unique strains, with n=12 mice from each strain. In addition, such DPOAE-screening data will be obtained at two ages in the same mice, ie, at 2 and 5 mo of age. The database created by these data will be analyzed in order to determine the 5th percentile of DPOAE levels in normal CBA-type mice and the 95th percentile in mice, such as the C57, with impaired cochlear function. The percentile data will be used to devise a standardized chart upon which data for individual mice undergoing mutagenesis can be plotted in order to determine if cochlear function is normal or impaired. In association with these experiments, a commercial instrument will be developed with a leading manufacturer of auditory-research equipment, which can be made available in the marketplace so that the scientific community will have access to the ability to determine the status of cochlear function in unknown mice. The second stage of the project, to be conducted in another group of mice from Years 1.5 to 3 of the study, is aimed at establishing a similar database for these same 40 mouse strains based on their susceptibility to noise-induced hearing loss. To accomplish this goal, following the acquisition of baseline DP-grams, at 3 mo mice will be exposed to a standard octave band noise known to cause permanent decrements in DPOAE levels, and then re-tested 2 wks later in order to document the effects of noise overexposure on cochlear function. Percentiles from these exposed mouse groups will form the basis of another standardized chart for determining the susceptibility of individual mice to acoustic overstimulation. Together, both projects will establish the usefulness of DPOAE testing for the purpose of developing simple and rapid screening methods of determining the status of cochlear function in individual mice. The resulting data will be made widely available on the internet in the form of databases and the relevant training manuals.