Mouse Models of Human Hearing Disorders

Kenneth   R.   Johnson

Abstract

Impairment of hearing is the most common sensory deficit in human populations. Most cases of human deafness are hereditary. Mutations in many different genes can affect the complex process of hearing. The mouse is an excellent model for studies of these hearing disorders because the anatomy, function, and hereditary abnormalities of the ear have been shown to be similar in both humans and mice. More than 100 spontaneous, chemically-induced, and genetically engineered mouse mutations have been discovered with hearing impairment many of these provide valuable models for both non-syndromic and syndromic forms of human deafness. So far, a total of 64 loci for human non-syndromic hearing impairment have been mapped, the genes responsible for 20 have been identified, and mouse models are available for 8 of these genes. More than 400 human syndromes have been described with associated hearing impairment, and about 80 genes have been identified. Mutations of homologous genes in the mouse have provided models for many of these syndromes. Studies of human hearing disorders and their mouse counterparts have contributed much to our understanding of the hearing process. For example, they have identified molecules (unconventional myosins, espins, and cadherins) that are important for the proper organization of hair cell stereocilia, ion transport and gap junction proteins that regulate endocochlear ion concentrations, and extracellular matrix proteins that compose acellular membranes important in auditory transduction. Genetically diverse inbred strains of mice provide models of age-related and noise-induced hearing loss and also provide a means to discover modifier genes by assessing mutant phenotypes on different strain backgrounds. With the new human and mouse genome initiatives now underway, the mouse will become an even more important animal model for hearing research.

Keywords: human hearing disorder, hereditary deafness, spontaneous mutation, genetically engineered, non syndromic, modifier genes

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