IGF-1R基因变异在特发性矮小症发病中的作用及机制

项目名称： IGF-1R基因变异在特发性矮小症发病中的作用及机制

项目编号： No.81460501

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨玉

作者单位： 江西省儿童医院

项目金额： 45万元

中文摘要： 特发性矮小症（ISS）病因不明，GH-IGF通路在发病中起重要作用，IGF-1R是调节该轴的效应分子。国外报道IGF-1R基因变异可引起正常身高变异和宫内发育迟缓儿的严重矮小，我们前期研究也提示IGF-1R基因SNP与ISS发病相关，但作用机制尚不清楚。为此，我们提出假说：IGF-1R基因变异引起蛋白功能改变从而影响IGF信号通路，导致ISS的发生。本实验将在ISS病例中筛选IGF-1R变异基因，通过IGF-1R 基因表达质粒的构建、鉴定，利用定向阻断IGF-1R基因的R细胞表达野生型和变异型IGF-1R，研究IGF-1R不同基因变异位点对编码蛋白功能的影响，并分析临床特点。从分子细胞结合临床等多方面探讨IGF-1R基因在ISS发病中的重要作用，从而阐明IGF-1R基因变异影响IGF信号通路导致ISS发病的调控机制，为揭示ISS的发生机制奠定基础，为ISS的防治提供新的思路。

中文关键词： 特发性矮小；胰岛素样生长因子1受体；基因变异；编码蛋白功能；生长发育

英文摘要： The pathogeny of idiopathic short stature（ISS）is still not undefined,and GH-IGF axis plays an important role in its pathogenesis.IGF-1R is the effector molecules to adjust the axis.According to foreign reports, IGF-1R genovariation may cause height variation of normal person and series nanism of intrauterine growth retardation.Our preliminary study also indicates that the IGF-1R gene SNP is related to the attack of ISS, but its mechanism of action is still not defined.For this purpose,we put forward the hypothesis: IGF-1R genovariation causes the change of protein function, thus affects GH-IGF signal pathway and causes the attack of ISS.In the experiment,IGF-1R mutant genes will be screened from the ISS cases. Through the structuring and assessment of the expression plasmid of IGF-1R ,we study the influence of different genovariation loca of IGF-1R on protein-encoding and analyze the clinical characteristics by using the R cell which means the directional blocking to IGF-1R gene to express the wild-type IGF-1R and the variant IGF-1R.We discuss the important role of IGF-1R played in the attach of ISS through molecular cell, clinical test, etc., thus to elaborate the regulation mechanism that IGF-1R genovariation affects IGF signal pathway and causes the attack of ISS, lay the solid foundation for revealing pathogenesis of ISS, and provide new thinking for preventing and treating the ISS.

英文关键词： idiopathic short stature;insulin-like growth factor-1 receptor;gene variation;protein-encoding function;growth and development