Otosclerosis affects more than 15 million people in this country, causing conductive hearing loss in approximately 10% of the affected individuals. A number of these people may also have sensorineural hearing loss. There is no recognized preventative measure for this genetic condition, and surgery can correct the conductive component of hearing loss but the sensorineural losses usually progress. Research has been hampered by the lack of an animal model. The proposed investigators have found what appears to be a genetic model in the inbred LP/J mouse. They wish to make a thorough characterization of this otosclerosis-like condition, comparing it with available human otosclerotic tissue. The progression of the mouse otosclerosis-like condition will be histologically examined with light, scanning- and transmission-electron microscopy, fluorochrome labelling of growing bone, histochemistry for lysosomal enzymes and immunohistochemistry for immunoglobulins. This disorder will be functionally traced with air-conducted electrocochleography. These coordinated measures will allow an accurate association of the structural, functional and biochemical changes. They will also provide a rational basis for future studies of the mechanism of the disease. Electrocochleography and histology will then be used to longitudinally assess the progress of the otosclerosis-like condition during various regimens of dietary sodium fluoride. The response of the LP/J mouse to fluorides will be compared to the responses of normal hearing CBA/J mice. Crossbreeding experiments will begin establishing the pattern of inheritance of this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021573-02
Application #
3402805
Study Section
Hearing Research Study Section (HAR)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Chole, R A; Faddis, B T; Chamberlain, S et al. (2001) Invasiveness of fibroblasts from experimental cholesteatomas. Otol Neurotol 22:15-7
Brodie, H A; Chang, P S; Chole, R A (1993) Dexamethasone inhibition of the development of dysplastic bony lesions in LP/J mice. Ann Otol Rhinol Laryngol 102:814-7
Adachi, K; Chole, R A; Yee, J (1991) Indomethacin inhibition of middle ear bone resorption. Arch Otolaryngol Head Neck Surg 117:267-9
Adachi, K; Chole, R A (1990) Inhibition of osteoclast recruitment at a local site by 1-hydroxyethylidene-1,1-bisphosphonate (HEBP). Ann Otol Rhinol Laryngol 99:738-41
Chole, R A; Chiu, M (1989) Cochlear hair cell stereocilia loss in LP/J mice with bone dysplasia of the middle ear. Ann Otol Rhinol Laryngol 98:461-5
Chole, R A; Chan, D E (1989) Rapid induction of localized bone resorption in the auditory bulla of the Mongolian gerbil, Meriones unguiculatus, by increased air pressure. Calcif Tissue Int 45:318-23
Lewis, E R; Henry, K R (1989) Transient responses to tone bursts. Hear Res 37:219-39
Henry, K R (1988) Effects of acoustic and sensory variables on masking tuning curves of the offset auditory brain-stem response in the rodent. Electroencephalogr Clin Neurophysiol 69:476-85
Chole, R A (1988) Osteoclasts in chronic otitis media, cholesteatoma, and otosclerosis. Ann Otol Rhinol Laryngol 97:661-6
Brodie, H A; Chole, R A (1987) The possible role of immunologic injury in the dysplastic bony lesion in LP/J mice. Am J Otolaryngol 8:342-50

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