title: Progressive hearing loss and increased susceptibility to noise-induced hearing loss in mice carrying a Cdh23 but not a Myo7a mutation.
abstract: 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.
authors.affiliation: MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Holme
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D000200:Action Potentials; D000375:Aging; D000818:Animals; D001309:Auditory Threshold; D015820:Cadherins / Q000235:genetics*; D002923:Cilia / Q000473:pathology; D004398:Dyneins; D005838:Genotype; D006198:Hair Cells, Auditory / Q000473:pathology / Q000648:ultrastructure; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006579:Heterozygote; D051379:Mice; D008808:Mice, Inbred CBA; D008818:Mice, Neurologic Mutants; D008855:Microscopy, Electron, Scanning; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D009622:Noise / Q000009:adverse effects
chemical_list: D015820:Cadherins; C499091:Cdh23 protein, mouse; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D009218:Myosins; D004398:Dyneins