Simmler M C, Cohen-Salmon M, El-Amraoui A, Guillaud L, Benichou J C, Petit C, Panthier J J
UMR 955 INRA de Génétique Moléculaire et Cellulaire, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort Cédex, France.
Nat Genet. 2000 Feb;24(2):139-43. doi: 10.1038/72793.
Genes specifically expressed in the inner ear are candidates to underlie hereditary nonsyndromic deafness. The gene Otog has been isolated from a mouse subtractive cDNA cochlear library. It encodes otogelin, an N-glycosylated protein that is present in the acellular membranes covering the six sensory epithelial patches of the inner ear: in the cochlea (the auditory sensory organ), the tectorial membrane (TM) over the organ of Corti; and in the vestibule (the balance sensory organ), the otoconial membranes over the utricular and saccular maculae as well as the cupulae over the cristae ampullares of the three semi-circular canals. These membranes are involved in the mechanotransduction process. Their movement, which is induced by sound in the cochlea or acceleration in the vestibule, results in the deflection of the stereocilia bundle at the apex of the sensory hair cells, which in turn opens the mechanotransduction channels located at the tip of the stereo-cilia. We sought to elucidate the role of otogelin in the auditory and vestibular functions by generating mice with a targeted disruption of Otog. In Otog-/- mice, both the vestibular and the auditory functions were impaired. Histological analysis of these mutants demonstrated that in the vestibule, otogelin is required for the anchoring of the otoconial membranes and cupulae to the neuroepithelia. In the cochlea, ultrastructural analysis of the TM indicated that otogelin is involved in the organization of its fibrillar network. Otogelin is likely to have a role in the resistance of this membrane to sound stimulation. These results support OTOG as a possible candidate gene for a human nonsyndromic form of deafness.
在内耳中特异性表达的基因是遗传性非综合征性耳聋的潜在病因。Otog基因是从小鼠耳蜗消减cDNA文库中分离出来的。它编码耳胶蛋白，这是一种N-糖基化蛋白，存在于覆盖内耳六个感觉上皮斑的无细胞膜中：在耳蜗（听觉感觉器官）中，位于柯蒂氏器上方的盖膜；在前庭（平衡感觉器官）中，位于椭圆囊和球囊斑上方的耳石膜以及三个半规管壶腹嵴上方的终帽。这些膜参与机械转导过程。它们的运动，由耳蜗中的声音或前庭中的加速度引起，导致感觉毛细胞顶端的静纤毛束发生偏转，进而打开位于静纤毛尖端的机械转导通道。我们试图通过构建Otog基因靶向敲除的小鼠来阐明耳胶蛋白在听觉和前庭功能中的作用。在Otog基因敲除小鼠中，前庭和听觉功能均受损。对这些突变体的组织学分析表明，在前庭中，耳胶蛋白是耳石膜和终帽锚定到神经上皮所必需的。在耳蜗中，对盖膜的超微结构分析表明，耳胶蛋白参与其纤维网络的组织。耳胶蛋白可能在该膜对声音刺激的抗性中起作用。这些结果支持OTOG作为人类非综合征性耳聋的一个可能候选基因。
