Among the five senses, hearing is fundamental for acquiring language, communication, and navigating through our environment. An estimated 28 million Americans are deaf or hearing impaired due to genetic factors, sound-induced trauma, aging or presbycusis, ototoxicity, and viral or bacterial infections. In order to investigate mechanisms involved in hearing dysfunction, and to develop new treatments and therapies for hearing dysfunction, the mouse is rapidly becoming the preferred experimental animal model. However, the anatomy and function of its cochlea has not been well characterized. Thus, the overall goal of this project is to improve our understanding of hearing by facilitating collaboration and multidisciplinary research on the mouse inner ear. Development of the Mouse Cochlea Database (MCD) will provide a web-based repository of comprehensive image and morphometric data on the mouse cochlea and custom-designed software tools to analyze these images. The overall hypothesis of this research is that development of the MCD will provide a new paradigm for learning and performing anatomical research on the cochlea in normal and certain hearing-impaired animals. Five integrated specific aims are proposed.
Aim 1 will image cochleas using thin- sheet laser imaging and celloidin sectioning from three strains of mice (CBA/J, C57BL/6, and C57BL/6 COL 4A5).
Aim 2 will develop multi-scale, multi-modal, and annotated 2D and 3D anatomical atlases of the cochlea in these mouse strains.
Aim 3 will develop a 3D coordinate system of the cochlea in order to generate virtual orthogonal cross sections of the scala media that are morphometrically analyzable. These cross-sections will be produced relative to the basilar membrane and mapped to the frequency/place map of the mouse cochlea.
Aim 4 will morphometrically analyze cochlear tissues in the virtual, orthogonal cross sections of the scala media in order to provide normative data and quantitative assessments of cochlear pathologies in age-related, hearing impaired mice, and in an X-linked mouse model of Alport syndrome.
Aim 5 will distribute data generated from experiments of the previous specific aims and provide online and offline software tools to morphometrically analyze cochlear tissues. Data will be web-based and available as images, searchable database files, movies, QuickTime VR, Acrobat 3D, stereolithography files for rapid prototyping, and stereoscopic files for VMRL displays. Development of the MCD will provide students and investigators with valuable anatomical resources of the cochlea in normal and of certain hearing impaired mice, and it will assist the research community face the challenges posed by the rapid growth in the amount and type of data on the mouse cochlea.
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