Contributions of mouse models to understanding of age- and noise-related hearing loss

Abstract

Once an oddity, mice have become the most widely used hearing research model. Their value for research in noise-induced hearing loss (NIHL) stems from their high vulnerability to noise and reduced variance of results, made possible by genetic standardization. To research in age-related hearing loss (ARHL), they offer economies of small size and a short lifespan, both of which reduce housing costs. Inbred mouse strains show a wide range of noise sensitivities and rates of hearing loss with age. These can be studied using classical genetic analysis, as well as hypothesis-driven experiments utilizing genetic engineering. Through such investigations, presently 3 loci have been identified to date that contribute to NIHL, 10 that promote ARHL, and at least 6 loci that promote both. The types of genes involved implicate homeostatic and protective mechanisms as key to the appearance of either type of pathology and support a causal link between injury and some apparent ARHL. While the majority of mouse ARHL models examined most closely resemble sensory ARHL, recent work has identified mice possessing the essential characteristics of neural and strial ARHL. Using these models, it should be possible to identify genes and alleles that promote the major forms of ARHL and their combinations.