Expression of Klotho protein in the inner ear.

The Klotho mouse is a recently developed model that exhibits phenotypes resembling human aging. We used this model to investigate sensorineural hearing loss from the point of view that it may be considered an issue of aging. Using reverse transcription-polymerase chain reaction, Western blotting and immunohistochemical staining, we were able to confirm klotho gene transcription and protein synthesis in the kidney and inner ear. Klotho protein was mainly expressed in the stria vascularis and spiral ligament of the inner ear and in the distal convoluted tubule of the kidney, likely serving a common function in the two organs, i.e., modulating ion transport. The threshold for the auditory brainstem response was significantly higher in Klotho mice than in wild-type mice, and wave I latencies were prolonged. On the other hand, Klotho mice exhibited a normal distribution of I-IV interpeak intervals. No obvious morphological abnormalities were detected in Klotho mice, although no expression of Klotho protein was detected, and there was an apparent hearing disorder. Taken together, these findings suggest that by contributing to the maintenance ion homeostasis in the endolymph, Klotho protein serves as a key mediator of auditory function.