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听力障碍，其病理生理机制尚未明确。然而，在过去的几年中，一些负责感音神经性听力损伤的基因已经被克隆，并且随着分子遗传学的发展，导致听力损伤的机制已经开始被阐明。本研究通过对行为异常和严重听力损失的突变小鼠进行评估，研究了人类感音神经性听力损失的病理生理学。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和听力能力之间的关联，我们在突变的纯合子和杂合子小鼠以及野生型动物中测定了这些特征。在纯合子中，耳蜗和球囊在出生后3个月退化。三个月大的杂合子表现出耳蜗的退化，而不是球囊。1月龄以上纯合子听性脑干诱发电位（ABR）各频率均无明显变化。与此相反，杂合子保留了一些听力敏锐度，直到一个月大，之后他们成为聋子。综上所述，听力损失是由常染色体显性方式传递，虽然异常运动是由常染色体隐性方式传递。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.