SBP2基因不同位点突变对硒蛋白合成的影响及其与甲状腺功能的相关性

项目名称： SBP2基因不同位点突变对硒蛋白合成的影响及其与甲状腺功能的相关性

项目编号： No.81500597

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 浮姣

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： SBP2是硒蛋白合成时硒代半胱氨酸掺入所必需的反式作用因子，其功能缺陷引起一类以生长发育迟缓和甲状腺功能异常为主要表现的临床综合征。目前研究表明SBP2缺陷患者的特殊甲状腺表型，很可能是包括脱碘酶在内的多种硒蛋白功能障碍的结果。然而，硒蛋白在甲状腺中的确切生物学作用却知之甚少，尤其是SBP2基因突变如何通过硒蛋白影响甲状腺的正常生理功能至今尚未见报道。我们的前期结果提示不同位点突变对SBP2功能的影响存在显著差异，部分揭示了SBP2缺陷患者病情严重程度存在显著差异的原因。本项目在此基础上，深入探讨SBP2基因不同位点突变对甲状腺功能的影响，并通过分析甲状腺滤泡细胞内硒蛋白的翻译效率和表达水平，阐明SBP2缺陷影响甲状腺功能的分子机制；同时结合甲状腺组织中硒蛋白的免疫组化分析，探究硒蛋白在甲状腺中的生物学功能。

中文关键词： 遗传学；SBP2基因突变；甲状腺功能异常；分子机制；硒蛋白

英文摘要： SECIS-binding protein 2 (SBP2) is a cis-acting factor required for the incorporation of selenocysteine during the biosynthesis of the 25 known selenoproteins. Mutations in SBP2 gene are responsible for a multisystem disorder characterized by delayed growth and distinct thyroid tests abnormalities. Studies showed that the thyroid phenotype of the disease probably resulted from the defective biosynthesis of many selenoproteins, including the three deiodinases. However, the biological functions of the selenoproteins in thyroid are currently poorly understood, and thus the effects of SBP2 gene mutations on the physiological function of the thyroid gland has not yet been reported. Our preliminary data shows that the functional significance varies between different mutations in SBP2 gene, which partially explains the complex phenotype of the disease. This project will aim to further clarify how different SBP2 mutations affect the thyroid function. By analyzing the synthesis of selenoproteins in thyroid follicular cells and thyroid tissues, we are to elucidate the molecular mechanism of thyroid abnormalities of SBP2 deficiency, and to explore the biological functions of selenoproteins in the thyroid gland.

英文关键词： genetics;SBP2 gene mutations;thyroid function abnormalities;molecular mechanism;selenoproteins