Identification and characterisation of mouse models for recessively inherited deafness.

听力损失影响了10%的澳大利亚人。大约每1000名儿童中就有1名出生时就是聋人。进行性听力障碍随着年龄的增长而发生，因此超过50%的75岁以上的人有严重的听力损失。耳聋的经济、社会和个人代价是巨大的。耳聋是由环境和/或遗传因素引起的。在大多数听力受损的儿童和年轻人中，潜在的原因是遗传的。众所周知，遗传易感性经常导致年龄相关性听力损失的发病时间和严重程度，以及对噪音和耳毒性药物的易感性。事实证明，很难确定导致耳聋的基因，特别是那些与年龄相关的听力损失以及对噪音和耳毒性药物敏感的基因。小鼠的耳朵与人类的耳朵非常相似，因此非常适合于人类耳聋的遗传和分子研究。澳大利亚拥有独特的突变小鼠资源，正在培育这些小鼠来发现隐性耳聋，这是最常见的遗传性听力损失类型。到目前为止，我们已经鉴定出10个患有隐性听力障碍的小鼠品系。其中5人患有与年龄相关的听力损失。我们已经在其中3个菌株中发现了基因突变，包括一个新的耳聋基因突变。另一种菌株具有一种新的耳聋基因突变，但尚未确定。我们建议继续对这些小鼠和其他小鼠的研究。我们将调查为什么这些基因的变化会导致听力损失，并详细确定遗传和环境因素如何导致年轻人和老年人的听力损失。这一结果将使我们能够为受影响的家庭提供更早的诊断和更好的咨询，从长远来看，我们相信我们的研究将使我们能够开发出改进或新颖的治疗方法，以延缓或预防耳聋。

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.