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Cell Biotechnology and Molecular Biology of Presbyacusis-related Gene and Its Clinical Application

老年性耳聋相关基因的细胞生物技术和分子生物学及其临床应用

基本信息

批准号：
08407054
负责人：
TAKASAKA Tomonori
金额：
$ 11.26万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08407054/
关键词：
Presbyacusis Mitochondrial DNA Aged mouse DNA mutation Hearing loss RT-PCR Digital hearing aid 遺伝子異常外有毛細胞血管条自然老化マウス高齢者のQOL

项目摘要

The inner ear composed of a post-mitotic stable tissue is a target organ for mitochondrial DNA (mtDNA) mutation. To determine whether mtDNA mutation is a predisposing factor in patients with sensorineural hearing loss (SNHL), we assessed the mtDNA^<4977> deletion from 60 patients with sensorineural hearing loss (SNHL) and 47 normal controls. All cases had no past history of ototoxic or noise exposure, middle ear disease, or other known etiological factors for SNHL.DNA specmiens extracted from peripheral blood leukocytes were used for detection of mtDNA^<4977> deletion by polymerase chain reaction. Patients with SNHL had a significantly high rate of the mtDNA^<4977> deletion than those of controls (75% vs 30%, p<0.0001). The detection rate of mtDNA^<4977> delection was significantly increased with the deterioration of the hearing threshold. Aging did not influence the detection rate of mtDNA^<4977> deletion in either the control or SNHL group. We have described high detection rates of the mtDNA^<4977> deletion in patients with idiopathic bilateral SNHL and propose that (at least) some of the advanced SNHL cases should be categorized as mitochondrial oxidative phosphorylation diseases. The present inference would offer novel possibilities for treatment and prevention of SNHL including presbycusis.A mutant mitochondrial DNA (mtDNA) was investigated in the aged cochlea of the animal model of presbycusis. The aged mice showed a significant deterioration of hearing compared with the young mice. The mtDNA with a 4802 bp deletion was highly detected in the aged cochlea (80%) whereas no mtDNA deletion was recognized in the young mice. These results indicates that the mtDNA deletion contributes to pathophysiological processes underlying presbycusis.

由有丝分裂后稳定的组织组成的内耳是线粒体DNA(MtDNA)突变的靶器官。为了确定mtDNA突变是否是感音神经性耳聋(SNHL)患者的易感因素，我们对60例感音神经性耳聋(SNHL)患者和47名正常对照的mtDNA4977&gt；缺失进行了检测。所有病例均无耳毒性或噪声暴露史、中耳疾病史或其他已知致病因素。从外周血白细胞中提取DNA谱用于聚合酶链式反应检测线粒体DNA4 977缺失。SNHL患者mtDNA4977&gt；缺失率显著高于对照组(75%vs30%，p&lt；0.0001)。随着听力阈值的降低，mtDNA4 977&gt；缺失率明显升高。增龄对对照组和SNHL组mtDNA4 977缺失的检出率均无影响。我们描述了在特发性双侧SNHL患者中mtDNA^&lt；4977&gt；缺失的高检出率，并建议(至少)部分晚期SNHL病例应被归类为线粒体氧化磷酸化疾病。本研究为包括老年性耳聋在内的SNHL的治疗和预防提供了新的可能性。在老年性耳聋动物模型中，研究了线粒体DNA的突变。与年轻小鼠相比，老年小鼠的听力明显下降。4802bp缺失的mtDNA在老年组高达80%，而在幼年组未发现缺失。这些结果表明线粒体DNA缺失参与了老年性耳聋的病理生理过程。