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 wildtype littermates. CDH23 is the first gene known to cause deafness in the human population to be linked with predisposition to noise-induced hearing loss.