Identification and characterisation of novel 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。另外，每1000人中就有1人在成年后患上听力损失。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。环境风险因素包括早产、感染和暴露在巨大噪音中。遗传因素包括许多基因中的一个基因的变化(突变)，这些基因的产物对正常的听力至关重要。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。也有人认为，遗传易感性经常导致年龄相关性听力损失的早期发病和严重程度。然而，很难确定导致耳聋的基因，因此我们对这些基因的作用知之甚少。小鼠的耳朵与人类的耳朵非常相似，在这一应用中，我们建议使用小鼠来识别和研究耳聋基因。澳大利亚拥有独特的老鼠资源，特别是为了发现遗传病而培育的老鼠。我们已经证明，在这些小鼠中，每1000只中就有一只患有类似于大多数新生儿和年轻人的遗传性听力损失。因此，这些小鼠为我们提供了一个发现新的耳聋基因的特殊机会，这将再次为我们提供更多关于我们如何听力的信息。我们将调查为什么这些基因的变化会导致听力损失，这些信息将使我们能够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。结果将使我们能够立即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的或新的治疗方法来延缓或预防耳聋。

Hearing loss affects 10% of Australians. Approximately 1 in 1000 children is born deaf. Another 1 in 1000 people develops hearing loss by adulthood. 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. Environmental risk factors include premature birth, infections and exposure to loud noise. Inherited factors include changes (mutations) in one of many genes whose products are essential for normal hearing. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also thought that genetic predisposition frequently contributes to the early onset and the severity of age-related hearing loss. However, it has been difficult to identify the genes causing deafness, and as a consequence we know relatively little about what these genes do. The mouse ear is very similar to the human ear and in this application we propose to use mice to identify and study deafness genes. Australia has a unique resource of mice that are being especially bred to uncover genetic diseases. We have shown that 1 in a 1,000 of these mice have a genetic hearing loss similar to that found in most newborns and young people. These mice therefore provide us with an exceptional opportunity to discover novel deafness genes, which again will provide us with more information about how we hear. We will investigate why changes in these genes causes hearing loss and this information will allow us to determine in detail how genetic and environmental factors lead to hearing loss in young and old. The results will immediately 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.