DPOAE PHENOTYPING OF COCHLEAR FUNCTION

点击翻译按钮获取中文摘要

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.