Identification and characterisation of mouse models for recessively inherited deafness.

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Hearing loss affects 10% of Australians. Approximately 1 in 1000 children are born deaf. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and-or inherited factors. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also known that genetic predisposition frequently contributes to the time of onset and the severity of age-related hearing loss, as well as susceptibility to noise and ototoxic drugs. It has proven difficult to identify the genes causing deafness, especially those genes associated with age-related hearing loss and susceptibility to noise and ototoxic drugs. The mouse ear is very similar to the human ear and therefore well suited to genetic and molecular studies of human deafness. Australia has a unique resource of mutagenised mice that are being bred to uncover recessive deafness, the most common type of inherited hearing loss. We have so far identified 10 mouse strains with recessive hearing impairment. 5 of the strains have an age-related hearing loss. We have identified the genetic mutation in 3 of the strains, including a mutation in a novel deafness gene. Another strain has a mutation in a novel deafness gene yet to be identified. We propose to continue the studies of these and additional mice. We will investigate why changes in these genes cause hearing loss and determine in detail how genetic and environmental factors lead to hearing loss in young and old. The results will allow us to offer earlier diagnosis and better counselling to affected families, and in the longer term we believe our research will enable us to develop improved or novel treatments to delay or prevent deafness.