Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Otorhinolaryngology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Lab Invest. 2018 Nov;98(11):1364-1374. doi: 10.1038/s41374-018-0083-y. Epub 2018 Jul 2.
Cadherin 11 (Cdh11), a member of the cadherin adhesion molecule family, is expressed in various regions of the brain as well as the head and ear. To gain further insights into the roles of Cdh11 in the development of the ear, we performed behavioral tests using Cdh11 knockout (KO) mice. KO mice showed reduced acoustic startle responses and increased thresholds for auditory brainstem responses, indicating moderate hearing loss. The auditory bulla volume and ratio of air-filled to non-air-filled space in the middle ear cavity were reduced in KO mice, potentially causing conductive hearing loss. Furthermore, residual mesenchymal and inflammatory cells were observed in the middle ear cavity of KO mice. Cdh11 was expressed in developing mesenchymal cells just before the start of cavitation, indicating that Cdh11 may be directly involved in middle ear cavitation. Since the auditory bulla is derived from the neural crest, the regulation of neural crest-derived cells by Cdh11 may be responsible for structural development. This mutant mouse may be a promising animal model for elucidating the causes of conductive hearing loss and otitis media.
钙黏蛋白 11(Cdh11)是钙黏蛋白黏附分子家族的成员,在大脑的各个区域以及头部和耳部表达。为了更深入地了解 Cdh11 在耳朵发育中的作用,我们使用 Cdh11 敲除(KO)小鼠进行了行为测试。KO 小鼠表现出较低的声惊跳反应和较高的听觉脑干反应阈值,表明存在中度听力损失。KO 小鼠的听泡体积和中耳腔充气与非充气空间的比例降低,可能导致传导性听力损失。此外,KO 小鼠的中耳腔中还观察到残余的间充质和炎症细胞。Cdh11 在即将发生囊泡形成之前的发育中问充质细胞中表达,表明 Cdh11 可能直接参与中耳囊泡形成。由于听泡来源于神经嵴,Cdh11 对神经嵴衍生细胞的调节可能与结构发育有关。这种突变小鼠可能是阐明传导性听力损失和中耳炎病因的有前途的动物模型。