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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC007588-02
Application #
7325778
Study Section
Special Emphasis Panel (ZRG1-MDCN-K (51))
Program Officer
Donahue, Amy
Project Start
2006-12-05
Project End
2010-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
2
Fiscal Year
2008
Total Cost
$216,068
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Santi, Peter A; Aldaya, Robair; Brown, Alec et al. (2016) Scanning Electron Microscopic Examination of the Extracellular Matrix in the Decellularized Mouse and Human Cochlea. J Assoc Res Otolaryngol 17:159-71
Hayashi, Hisamitsu; Schrott-Fischer, Annelies; Glueckert, Rudolf et al. (2015) Erratum to: Molecular organization and fine structure of the human tectorial membrane: is it replenished? Cell Tissue Res 362:689-90
Hayashi, Hisamitsu; Schrott-Fischer, Annelies; Glueckert, Rudolf et al. (2015) Molecular organization and fine structure of the human tectorial membrane: is it replenished? Cell Tissue Res 362:513-27
Schmitz, Heather M; Johnson, Shane B; Santi, Peter A (2014) Kanamycin-furosemide ototoxicity in the mouse cochlea: a 3-dimensional analysis. Otolaryngol Head Neck Surg 150:666-72
Johnson, Shane B; Cureoglu, Sebahattin; O'Malley, Jennifer T et al. (2014) Comparison of traditional histology and TSLIM optical sectioning of human temporal bones. Otol Neurotol 35:1145-9
Santi, Peter A; Johnson, Shane B (2013) Decellularized ear tissues as scaffolds for stem cell differentiation. J Assoc Res Otolaryngol 14:3-15
Buytaert, Jan A N; Johnson, Shane B; Dierick, Manuel et al. (2013) MicroCT versus sTSLIM 3D imaging of the mouse cochlea. J Histochem Cytochem 61:382-95
Kopecky, Benjamin; Johnson, Shane; Schmitz, Heather et al. (2012) Scanning thin-sheet laser imaging microscopy elucidates details on mouse ear development. Dev Dyn 241:465-80
Pan, Ning; Jahan, Israt; Kersigo, Jennifer et al. (2011) Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res 275:66-80
Santi, Peter A (2011) Light sheet fluorescence microscopy: a review. J Histochem Cytochem 59:129-38

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