MOLECULAR BASIS OF OTOPATHOLOGY

耳病理学的分子基础

• 批准号: 2749270
• 负责人: MICHAEL J. MCKENNA
• 金额: $ 32.85万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2749270
• 关键词: audiometry; clinical research; collagen; disease /disorder etiology; gene deletion mutation; human data; human genetic material tag; human subject; human tissue; measles; measles virus; mitochondrial DNA; molecular genetics; nucleic acid sequence; osteogenesis imperfecta; otosclerosis; point mutation; presbycusis; temporal bone; virus RNA

DESCRIPTION: Two specific aims were delineated: First, morphological, immunohistochemical, and molecular genetic evidence suggest that measles virus is present in otosclerotic lesions. Paramyxoviruses have been implicated in other osseous dysplasias (e.g. Paget's disease). The investigators plan to search for measles virus RNA in otosclerotic temporal bones. The applicant wi draw upon the extensive archival collection at the Massachusetts Eye and Ear Infirmary (MEEI) which includes 205 sets of otosclerotic temporal bones. Recently, the osteogenesis imperfecta (OI) associated gene COL 1A1 has been implicated in otosclerosis. The hypothesis is that otosclerosis represents a minor variant of OI and possesses a similar dysfunction in type 1 collagen. They have in hand samples from 220 individuals from 65 families with otosclerosis. The second line of investigation involves mtDNA mutations associated with presbycusis. The MEEI archival temporal bone collection contains 142 sets of temporal bones with various types of presbycusis (28 sensory, 70 neural, 44 strial). Comprehensive audiological profiles are available. Sensorineural hearing loss is present in virtually all known varieties of mitochondrial dysfunction. Mitochondrial mutations appear to accumulate with advancing age. The investigators plan to search for a variety of point mutations as well as sequential deletions in mtDNA obtained from their archival collection. Collection of audiological data from patients with known mitochondrial mutatio will also be undertaken.

描述：划定了两个具体目标：第一，形态学， 免疫组织化学和分子遗传学证据表明麻疹 病毒存在于耳状病变中。 帕托病毒已经存在 与其他骨肌发育不良有关（例如paget病）。 这 研究人员计划在耳效性时间上寻找麻疹病毒RNA 骨头。 申请人WI借鉴了广泛的档案收藏 马萨诸塞州的眼睛和耳科医院（MEEI），其中包括205套 耳硬膜硬化颞骨。 最近，成骨不完美（OI） 相关的基因Col 1a1已与耳鼻喉性有关。 假设 是耳效性代表了OI的次要变体，并具有 类型1胶原蛋白的类似功能障碍。 他们有220个手工样本 来自65个耳鼻喉病的患者。 第二道调查涉及与MTDNA突变有关 长老会。 MEEI档案临时骨收集包含142套 具有各种各样的长期骨的颞骨（28个感觉，70个神经， 44弦）。 提供全面的听力学概况。 几乎所有已知品种都存在感官听力损失 线粒体功能障碍。 线粒体突变似乎积累 随着年龄的增长。 调查人员计划寻找各种各样的点 MTDNA中的突变以及从其获得的顺序缺失 档案收藏。 来自患者的听力学数据 还将进行已知的线粒体突变。