DISTORTION PRODUCT OTOACOUSTIC EMISSIONS--COCHLEAR FUNCT

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表型分型方法。 第1-1.5年的初步实验重点是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DP图的形式在三个水平上获得2f 1-f2 DPOAE，DP图将在5.6至48.5 kHz（f2=60 kHz）的几何平均值范围内的频率范围内以每倍频程10个点进行测试。将从代表40个独特品系的小鼠的双耳记录这些测量值，每个品系n=12只小鼠。此外，将在相同小鼠的两个年龄（即2月龄和5月龄）获得此类DPOAE筛选数据。 将分析由这些数据创建的数据库，以确定正常CBA型小鼠中DPOAE水平的第5百分位数和耳蜗功能受损小鼠（如C57）中的第95百分位数。 百分位数数据将用于设计标准化图表，在该图表上可以绘制经历诱变的个体小鼠的数据，以确定耳蜗功能是正常的还是受损的。 与这些实验相关的是，将与一家领先的耳蜗研究设备制造商开发一种商业仪器，这种仪器可以在市场上提供，以便科学界能够确定未知小鼠的耳蜗功能状况。 该项目的第二阶段将在另一组小鼠中进行，从研究的第1.5年到第3年，旨在根据这些小鼠对噪声引起的听力损失的易感性，为这40种小鼠品系建立类似的数据库。 为了实现这一目标，在获得基线DP图之后，在3个月时，将小鼠暴露于已知引起DPOAE水平永久性降低的标准倍频程噪声，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形成用于确定个体小鼠对声学过度刺激的敏感性的另一标准化图表的基础。这两个项目将共同建立DPOAE测试的有用性，以开发确定单个小鼠耳蜗功能状态的简单快速筛选方法。 由此产生的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.