Identification and characterisation of novel mouse models for recessively inherited deafness.

听力损失影响着10%的澳大利亚人。大约每1000个儿童中就有1个天生耳聋。另有千分之一的人在成年后出现听力损失。随着年龄的增长，听力损害会逐渐加重，因此75岁以上的人中有50%以上有严重的听力损失。耳聋造成的经济、社会和个人成本是巨大的。耳聋是由环境和遗传因素引起的。环境风险因素包括早产、感染和暴露在噪音中。遗传因素包括其产物对正常听力至关重要的许多基因之一的改变（突变）。在大多数患有听力障碍的儿童和年轻人中，潜在的原因是遗传的。人们还认为，遗传易感性经常导致与年龄有关的听力损失的早期发病和严重程度。然而，识别导致耳聋的基因一直很困难，因此我们对这些基因的作用知之甚少。老鼠的耳朵与人的耳朵非常相似，在这个应用中，我们建议用老鼠来识别和研究耳聋基因。澳大利亚有一种独特的老鼠资源，这些老鼠是专门用来发现遗传疾病的。我们已经证明，每1000只老鼠中就有1只会有遗传性听力损失，这与大多数新生儿和年轻人的情况相似。因此，这些老鼠为我们提供了一个特殊的机会来发现新的耳聋基因，这将再次为我们提供更多关于我们如何听到的信息。我们将研究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是如何导致年轻人和老年人的听力损失的。研究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.