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.
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