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

隐性遗传性耳聋新型小鼠模型的鉴定和表征。

• 批准号: nhmrc : 284550
• 负责人: A/Pr Hans-Henrik Dahl
• 金额: $ 33.66万
• 依托单位: Murdoch Childrens Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/identification-characterisation-novel-inherited-deafness/81061
• 关键词: Identification; characterisation; novel; mouse; models

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.

听力损失影响了10%的澳大利亚人。大约每1000名儿童中就有一名是天生耳聋的。另有1/1000的人在成年后出现听力损失。随着年龄的增长，听力障碍会逐渐加重，因此超过50%的75岁以上的人患有严重的听力损失。耳聋造成的经济、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、感染和暴露于巨大噪音。遗传因素包括许多基因之一的变化（突变），这些基因的产物对正常听力至关重要。在大多数儿童和青少年中，听力障碍的根本原因是遗传。人们还认为，遗传易感性往往导致与年龄有关的听力损失的早期发作和严重程度。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。小鼠耳朵与人耳非常相似，在本申请中，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，这些老鼠被特别培育以发现遗传疾病。我们已经证明，这些小鼠中每1,000只中就有1只具有与大多数新生儿和年轻人相似的遗传性听力损失。因此，这些小鼠为我们提供了一个发现新的耳聋基因的绝佳机会，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如何导致年轻人和老年人的听力损失。研究结果将立即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更好的或新的治疗方法来延迟或预防耳聋。