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一种常见的临床疾病，其病理生理机制尚不清楚。然而，随着分子遗传学的发展，一些与感音神经性听力障碍相关的基因已被克隆，导致听力障碍的机制也开始被阐明。我们通过对行为异常、听力严重丧失的突变小鼠的评价，研究了人类感音神经性耳聋的病理生理学。Wrigger Mouse Sagami(WMS)是一种自发突变的具有神经上皮缺陷的突变株。这些动物的特征是与常染色体隐性基因有关的异常运动。为了确定内耳组织学与听力之间的关联，我们分析了突变纯合子和杂合子小鼠以及野生型动物的这些特征。在纯合子中，出生后三个月耳蜗球囊变性。三个月大的杂合子在耳蜗处表现出变性，而在球囊中没有。在1月龄及以上的纯合子中，未观察到明显的听性脑干诱发反应(ABR)。相比之下，杂合子在出生后1个月内仍保持一定的听力，之后耳聋。综合起来，听力损失是以常染色体显性遗传方式传递的，而异常运动是通过常染色体隐性遗传方式传递的。这些发现表明，WMS小鼠可能提供了一个很好的模型，将有助于识别人类的耳聋基因。

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.