Ildr1b is essential for semicircular canal development, migration of the posterior lateral line primordium and hearing ability in zebrafish: implications for a role in the recessive hearing impairment DFNB42
Ildr1b is essential for semicircular canal development, migration of the posterior lateral line primordium and hearing ability in zebrafish: implications for a role in the recessive hearing impairment DFNB42
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Ildr1b 对于斑马鱼的半规管发育、后侧线原基的迁移和听力至关重要：对隐性听力障碍 DFNB42 中作用的影响
DOI：
10.1093/hmg/ddu340
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发表时间：
2014
影响因子：
3.5
通讯作者：
Wang Lei
中科院分区：
文献类型：
--
作者：
Sang Qing;Zhang Junyu;Feng Ruizhi;Wang Xu;Li Qiaoli;Zhao Xinzhi;Xing Qinghe;Chen Weiyu;Du Jiulin;Sun Shan;Chai Renjie;Liu Dong;Jin Li;He Lin;Li Huawei;Wang Lei
免疫球蛋白样结构域包含受体1(ILDR1)基因是首先在淋巴瘤细胞中发现的一个功能不全的基因。最近，ILDR1被发现与常染色体隐性遗传性听力障碍DFNB42有关。携带ILDR1突变的患者导致双侧非进行性中度至重度感音神经性听力损害。然而，ILDR1相关性听力损失的病因和机制仍有待阐明。为了揭示DFNB42耳聋的发病机制，我们采用吗啡注射技术建立了anildr1b变异型斑马鱼模型，发现ildr1b变型斑马鱼表现为听力障碍和游泳不平衡，内耳半规管发育迟缓。基因表达谱和实时荧光定量聚合酶链式反应显示，在idr1b变异斑马鱼中，atp1b2b(编码Na+/K+转运，β2b多肽)的表达下调。我们发现，在转基因斑马鱼中注射atp1b2bmRNA可以挽救半规管发育迟缓的表型。此外，ildr1b变异斑马鱼由于侧线原基迁移的中断而减少了侧线神经肥大细胞的数量。原位杂交显示，在ildr1b变异斑马鱼的后外侧线原基中，减弱的成纤维细胞生长因子信号和趋化因子受体4b(Cxcr4b)和趋化因子受体7b(Cxcr7b)参与了这一过程。我们得出结论，Ildr1b对内耳和侧线系统的发育至关重要。本研究首次为Ildr1b在体内的作用机制提供了证据，并为DFNB42的病理机制提供了新的线索。
Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Recently,ILDR1has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients withILDR1mutations cause bilateral non-progressive moderate-to-profound sensorineural hearing impairment. However, the etiology and mechanism ofILDR1-related hearing loss remains to be elucidated. In order to uncover the pathology of DFNB42 deafness, we used the morpholino injection technique to establish anildr1b-morphant zebrafish model.Ildr1b-morphant zebrafish displayed defective hearing and imbalanced swimming, and developmental delays were seen in the semicircular canals of the inner ear. The gene expression profile and real-time PCR revealed down-regulation ofatp1b2b(encoding Na+/K+transporting, beta 2b polypeptide) inildr1b-morphant zebrafish. We found that injection ofatp1b2bmRNA intoildr1b-knockdown zebrafish could rescue the phenotype of developmental delay of the semicircular canals. Moreover,ildr1b-morphant zebrafish had reduced numbers of lateral line neuromasts due to the disruption of lateral line primordium migration.In situhybridization showed the involvement of attenuated FGF signaling and the chemokine receptor 4b (cxcr4b) and chemokine receptor 7b (cxcr7b) in posterior lateral line primordium ofildr1b-morphant zebrafish. We concluded that Ildr1b is crucial for the development of the inner ear and the lateral line system. This study provides the first evidence for the mechanism of Ildr1b on hearingin vivoand sheds light on the pathology of DFNB42.