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

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可以在人体材料中进行研究。因此，遗传性内耳缺陷动物模型是研究人类内耳畸形复杂图像的基本机制的有用模型。我们发现了一种新的突变小鼠，它是C3H/He群体中的一种自发突变。这些动物表现出转圈、摇头和多动等异常行为。该基因是常染色体隐性遗传，预计在第11号染色体上有单基因突变。分析了该新突变小鼠的内耳听力和组织学特征。听力学结果显示，在出生11天到117天的纯合子中，没有任何可记录到的听性脑干反应(ABR)。最显著的形态学发现是耳蜗外毛细胞和斑区毛细胞的立体纤毛排列紊乱，但毛细胞细胞质包括神经末梢已完全发达。随后发生外毛细胞和囊状毛细胞的年龄依赖性退化和囊状耳锥的解体。由于没有观察到中枢神经系统的形态异常，这些小鼠的异常行为主要与前庭的形态异常有关。由于这种动物被认为具有单基因异常，因此对这种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的性质的重要信息。

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.