Progressive hearing loss and increased susceptibility to noise-induced hearing loss in mice carrying a Cdh23 but not a Myo7a mutation.

Exposure to intense noise can damage the stereocilia of sensory hair cells in the inner ear. Since stereocilia play a vital role in the transduction of sound from a mechanical stimulus into an electrical one, this pathology is thought to contribute to noise-induced hearing loss. Mice homozygous for null mutations in either the myosin VIIa ( Myo7a) or cadherin 23 ( Cdh23) genes are deaf and have disorganized stereocilia bundles. We show that mice heterozygous for a presumed null allele of Cdh23 ( Cdh23(v)) have low- and high-frequency hearing loss at 5-6 weeks of age, the high-frequency component of which worsens with increasing age. We also show that noise-induced hearing loss in 11-12-week-old Cdh23(v) heterozygotes is two times greater than for wild-type littermates. Interestingly, these effects are dependent upon the genetic background on which the Cdh23(v) mutation is carried. Noise-induced hearing loss in 11-12-week-old mice heterozygous for a null allele of Myo7a ( Myo7a(4626SB)) is not significantly different from wild-type littermates. CDH23 is the first gene known to cause deafness in the human population to be linked with predisposition to noise-induced hearing loss.