Identification and characterisation of mouse models for recessively inherited deafness.

隐性遗传性耳聋小鼠模型的鉴定和表征。

• 批准号: nhmrc : 436944
• 负责人: A/Pr Hans-Henrik Dahl
• 金额: $ 46.14万
• 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: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/identification-characterisation-mouse-inherited-deafness/96085
• 关键词: Identification; characterisation; mouse; models; recessively

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.

10% 的澳大利亚人患有听力损失。大约千分之一的儿童出生时耳聋。随着年龄的增长，听力会逐渐受损，超过 50% 的 75 岁以上的人有严重的听力损失。耳聋造成的经济、社会和个人损失是巨大的。耳聋是由环境和/或遗传因素引起的。大多数患有听力障碍的儿童和青少年的根本原因是遗传。人们还知道，遗传倾向常常会影响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敏感性。事实证明，识别导致耳聋的基因很困难，尤其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相关的基因。小鼠耳朵与人耳非常相似，因此非常适合人类耳聋的遗传和分子研究。澳大利亚拥有独特的诱变小鼠资源，这些小鼠正在被培育以发现隐性耳聋，这是最常见的遗传性听力损失类型。迄今为止，我们已经鉴定出 10 种具有隐性听力障碍的小鼠品系。其中 5 株存在与年龄相关的听力损失。我们已经鉴定出其中 3 种菌株的基因突变，其中包括一种新型耳聋基因的突变。另一种菌株的一种新的耳聋基因发生了突变，目前尚未确定。我们建议继续对这些小鼠和其他小鼠进行研究。我们将研究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。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的或新颖的治疗方法来延迟或预防耳聋。