Analysis of Human Sensorineural Hearing Loss by Genetic Study of Mouse with Inner Ear Anomaly

感音神经性听力障碍是临床上常见的疾病，其病理生理机制尚不明确。然而，近年来一些与感音神经性听力障碍有关的基因已被克隆出来，随着分子遗传学的发展，听力障碍的机制已开始被阐明。我们通过对行为异常和严重听力损失的突变小鼠进行评估，研究了人感音神经性听力损失的病理生理。扭鼠Sagami （WMS）是一种具有神经上皮缺陷的自发突变株。这些动物的特征是与常染色体隐性基因相关的异常运动。为了确定内耳组织学与听力能力之间的关系，我们在突变纯合子和杂合子小鼠以及野生型动物中分析了这些特征。在纯合子中，耳蜗和耳囊在出生3个月后退化。三个月大的杂合子显示耳蜗变性，而非耳蜗。1月龄及以上纯合子无明显听觉脑干诱发反应（ABR）。相比之下，杂合子在一个月大之前还保留着一些听力敏锐度，之后就会失聪。综上所述，听力损失是通过常染色体显性方式传播的，而异常运动是通过常染色体隐性方式传播的。这些发现表明，WMS小鼠可能为识别人类耳聋基因提供了一个很好的模型。

Pathophysiology of sensorineural hearing impairment which is acommon clinical disorder remains yet to be determined. However, some genes responsible for sensorineural hearing impairment have been cloned for the last several years and the mechanism causing hearing impairment has been started to be clarified with the advent of development of molecular genetics. We studied here pathophysiology of human sensorineural hearing loss by evaluating the mutant mouse with abnormal behavior and severe hearing loss.Wriggle Mouse Sagami (WMS) is a spontaneous mutant strain with neuroepithelial defects. These animals are characterized by abnormal movements linked to an autosomal recessive gene. To determine the association between inner ear histology and hearing ability, we assayed these characteristics in mice homozygous and heterozygous for the mutation, as well as in wild-type animals. In homozygotes, the cochlea and saccule degenerated three months after birth. Three-month-old heterozygotes demonstrated degeneration in the cochlea, not in the saccule. No obvious auditory brainstem evoked response (ABR) was observed at any frequency in homozygotes aged one month and older. In contrast, the heterozygotes retained some hearing acuity until the age of one month, after which they became deaf.Taken together, loss of hearing is transmitted by an autosomal dominant manner although abnormal movements are transmitted by an autosomal recessive manner. These findings suggest that WMS mice may provide a good model that will be useful in identifying deafness genes in humans.