权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Physiological and histological study of mouse inner ear with hearing loss and dysequilibrium caused by single gene deletion.

单基因缺失所致听力损失及平衡失调小鼠内耳生理组织学研究

基本信息

批准号：
01480405
负责人：
KITAMURA Ken
金额：
$ 2.05万
依托单位：
Jichi Medical School (1991)The University of Tokyo (1989-1990)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

Inner ear disorders of hereditary origin are fairly common in humans. A full evaluation of these disorders cannot always, however, be studied in human material. Therefore, animals with hereditary inner ear defects are useful models for studying the basic mechanism in the complex picture of inner ear abnormality in humans. We uncovered a strain of new mutant mice which arose as a spontaneous mutation in the C3H/He stock. The animals show abnormal behavior such as circling, head-tossing and hyperactivity. The gene is autosomal recessive and a single gene mutation is expected on chromosome 11. The hearing ability and histological characteristics of the inner ear of this new mutant mice were analyzed. The audiological findings exhibited no recordable auditory brain stem response (ABR) in any homozygotes at ages ranging from 11 days to 117 days. The most striking morphological findings were disarray of the stereocilia of the outer hair cells of the cochlea and hair cells of the maculae, although hair cell cytoplasm became fully developed, including the nerve terminals. Age-dependent degeneration of the outer hair cells and saccular hair cells and disintegration of the saccular otoconia subsequently occurred. Because no morphological abnormality was observed in the central nervous system, the abnormal behavior in these mice was primarily correlated with morphological abnormalities of the vestibule. As this animal is expected to have a single gene abnormality, molecular genetic studies on this animal can provide important information on the nature of histological changes of the hair cell from mode of gene action.

遗传性内耳疾病在人类中相当常见。然而，对这些疾病的全面评估并不总是能够在人体材料中进行研究。因此，具有遗传性内耳缺陷的动物是研究人类内耳异常复杂情况的基本机制的有用模型。我们发现了一种新的突变小鼠品系，它是 C3H/He 种群中自发突变产生的。这些动物表现出异常行为，如转圈、摇头和多动。该基因为常染色体隐性遗传，预计在11号染色体上有单基因突变。对这种新突变小鼠的听力和内耳组织学特征进行了分析。听力学结果显示，11 天至 117 天的纯合子中没有可记录的听觉脑干反应 (ABR)。最引人注目的形态学发现是耳蜗外毛细胞和黄斑毛细胞的静纤毛紊乱，尽管毛细胞的细胞质（包括神经末梢）已完全发育。随后发生外毛细胞和囊状毛细胞的年龄依赖性变性以及囊状耳石的崩解。由于中枢神经系统没有观察到形态异常，因此这些小鼠的异常行为主要与前庭的形态异常相关。由于这种动物预计有单一基因异常，因此对该动物的分子遗传学研究可以从基因作用模式提供有关毛细胞组织学变化性质的重要信息。