Analyses of Type XI Collagen in Craniofacial Development and the Auditory System

Stickler综合征是一种显性骨软骨发育不良，与编码XI型胶原多肽亚基的三个基因COL2A1、COL11A1和COL11A2中的任何一个基因突变有关。为了更好地了解这些基因突变引起的感音神经性听力损失的发病机制，我们检测了Col11a1和Col11a2在小鼠内耳中的表达。结果显示在内耳和前庭迷路的软组织元素中弥漫性表达。我们还对这些基因突变的小鼠模型进行了表征，以确定它们对内耳和听觉系统发育的贡献。我们的研究结果表明，携带Col11a1或Col11a2纯合子功能零突变的小鼠不会表现出明显的耳蜗结构异常。我们得出结论，这些胶原蛋白基因的突变可能会改变耳蜗及其神经感觉器官的生物力学特性，从而导致声音机械传导的改变和感音神经性听力损失。我们正计划利用听力学和电生理学技术在人类身上验证这一假设。- Stickler综合征，耳聋，内耳，胶原蛋白，听力损失，分子遗传学

Stickler syndrome is a dominant osteochondrodysplasia associated with mutations in any one of the three genes encoding the polypeptide subunits of type XI collagen: COL2A1, COL11A1, and COL11A2. In order to better understand the pathogenesis of sensorineural hearing loss caused by mutations in these genes, we have examined the expression of Col11a1 and Col11a2 within the inner ears of mice. The results demonstrate diffuse expression within the soft tissue elements of the inner ear and vestibular labyrinth. We have also characterized mouse models harboring mutations in these genes in order to define their contribution to development of the inner ear and auditory system. Our results demonstrate that mice carrying homozygous functional null mutations for either Col11a1 or Col11a2 do not manifest obvious structural abnormalities of the cochlea. We conclude that mutations in these collagen genes likely alter the biomechanical properties of the cochlea and its neurosensory organs, thus leading to altered sound mechanotransduction and sensorineural hearing loss. We are planning to test this hypothesis in humans using audiologic and electrophysiologic techniques. - Stickler syndrome, deafness, inner ear, collagen, hearing loss, molecular genetics