DPOAE PHENOTYPING OF COCHLEAR FUNCTION

计划中的研究旨在根据小鼠外周耳的功能状态开发一种快速的表型方法。1-1.5年级的初始实验侧重于开发一种使用畸变产物耳声发射（dpoae）的方案，该方案适用于筛选大量小鼠的耳蜗异常。为了实现这一目标，将以dpgram的形式在三个级别上获得2f1-f2 dpoae，这些dpoae将在5.6至48.5 kHz （f2=60 kHz）的几何平均频率范围内以每八度程10个点进行测试。这些测量将从代表40个独特品系的小鼠双耳记录，每个品系n=12只小鼠。此外，这种dpoae筛选数据将在同一只小鼠的两个年龄阶段获得，即2月龄和5月龄。将对这些数据创建的数据库进行分析，以确定正常cba型小鼠的第5百分位DPOAE水平，以及耳蜗功能受损小鼠（如C57）的第95百分位DPOAE水平。百分位数数据将用于设计一个标准化的图表，在此基础上，可以绘制出接受诱变的单个小鼠的数据，以确定耳蜗功能是正常还是受损。与这些实验相结合，将与一家领先的听觉研究设备制造商合作开发一种商业仪器，这种仪器可以在市场上获得，以便科学界能够确定未知小鼠的耳蜗功能状态。该项目的第二阶段将在研究的第1.5年至第3年的另一组小鼠中进行，目的是根据这40种小鼠对噪音引起的听力损失的易感性，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，将3个月大的小鼠暴露于已知会导致DPOAE水平永久性下降的标准倍频噪声中，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。来自这些暴露小鼠组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学过度刺激的易感性。总之，这两个项目将建立DPOAE测试的有效性，目的是开发简单快速的筛选方法来确定单个小鼠耳蜗功能的状态。所得数据将以数据库和有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.