CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea
CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea
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DOI：
10.1136/jmg.2005.034397
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Usami, S.
中科院分区：
文献类型：
--
作者：
Oshima, A.;Suzuki, S.;Usami, S.
背景资料：Mu-crystallin（Mu-crystallin，MUM）是一种Taxion特异性晶体蛋白，也是一种NADP调节的甲状腺激素结合蛋白，在非综合征性耳聋患者中发现MUM的C端有两处突变。将突变的μ-晶状体蛋白的T3结合活性与野生型μ-晶状体蛋白的T3结合活性进行比较，因为已知μ-晶状体蛋白与T3结合蛋白相同。要探索的网站在耳蜗内的mu-crystallin的功能，其在小鼠耳蜗的本地化进行了调查immunocytochemically使用一种特异性antibody.Results：一个突变体被证明是没有结合能力的T3，这表明，MARM突变引起听觉功能障碍，通过甲状腺激素结合性能。免疫细胞化学结果表明，mu-crystallin分布在Ⅱ型纤维细胞的外侧壁，这是已知的含有Na，K-ATPase.Conclusions：MANTM突变可能会导致听觉功能障碍，通过甲状腺激素结合作用的纤维细胞的耳蜗。mu-Crystallin可能与Na，KATP酶一起参与钾离子再循环系统。未来的动物实验将是必要的，以确认之间的因果关系Na，K-ATP酶，T3和耳聋。
Background: In a search for mutations of mu-crystallin (CRYM), a taxion specific crystalline which is also known as an NADP regulated thyroid hormone binding protein, two mutations were found at the C-terminus in patients with non-syndromic deafness.Objective: To investigate the mechanism of hearing loss caused by CRYM mutationsMethods: T3 binding activity of mutant mu-crystallin was compared with that of wild-type mu-crystallin, because mu-crystallin is known to be identical to T3 binding protein. To explore the sites within the cochlea where mu-crystallin is functioning, its localisation in the mouse cochlea was investigated immunocytochemically using a specific antibody.Results: One mutant was shown to have no binding capacity for T3, indicating that CRYM mutations cause auditory dysfunction through thyroid hormone binding properties. Immunocytochemical results indicated that mu-crystallin was distributed within type II fibrocytes of the lateral wall, which are known to contain Na, K-ATPase.Conclusions: CRYM mutations may cause auditory dysfunction through thyroid hormone binding effects on the fibrocytes of the cochlea. mu-Crystallin may be involved in the potassium ion recycling system together with Na, KATPase. Future animal experiments will be necessary to confirm a causal relation between Na,K-ATPase, T3, and deafness.