小鼠Lrp5基因表达调控的研究

发布时间：2018-02-23 16:37

本文关键词： LDL受体相关蛋白5 LRP5基因基因表达调控启动子转录因子荧光素酶报告基因分析系统　出处：《山东大学》2005年博士论文　论文类型：学位论文

【摘要】：低密度脂蛋白受体相关蛋白5(low densjty lipoprotein receptor re]ated protein5,LRP5)是细胞表面的受体蛋白,属于低密度脂蛋白受体家族,可通过与相应配体结合参与受体介导的细胞内吞作用而实现多方面的功能。LRP5基因全长cDNA是1998年分别由Merck实验室和Bayer研究中心克隆的。Merck实验室是在建立胰岛素依赖性糖尿病基因候选区域物理图和转录图时从肝脏的cDNA文库中分离得到LRP5基因的。Bayer实验室是在分离成骨细胞发育相关基因时从成骨细胞cDNA文库中分离到该基因的。研究标明LRP5基因丧失功能突变(包括错义,无义及移码突变)导致骨质疏松-假性神经胶质瘤综合征(Osteoporosis-Pseudoglioma Syndrome,OPS),该综合征的主要临床表现为幼年型骨质疏松和假性神经胶质瘤,并发现携带LRP5基因突变的杂合子骨密度显著低于对照组。Lrp5基因敲除小鼠分析表明,纯合子小鼠表现为类似于人类OPS表型,杂合子小鼠表现为明显的骨质疏松。另一方面,LRP5基因的获得功能突变导致高骨密度症。这些结果提示LRP5基因在骨密度调节过程中起重要作用。LRP5广泛存在于人体许多组织细胞表面,包括肝、胰、小肠、心、肺、骨骼肌、肾、脾、脑、外周血细胞等。尽管LRP5基因在多种组织中表达,但基因突变所引起的表型效应仅局限在骨骼和眼,其它组织器官发育正常。目前关于LRP5基因的其它方面功能、表达调控机制以及其在骨密度调节过程中的作用机制尚不清楚,阐明该基因表达的调控机制将有助于理解LRP5基因的功能。为此,本课题进行了以下几个方面的研究:
[Abstract]:The low density lipoprotein receptor associated protein (5low densjty lipoprotein receptor re) ated protein 5 (LRP5) is a receptor protein on the cell surface and belongs to the low density lipoprotein receptor family. The full-length cDNA of the LRP5 gene, cloned by the Merck Laboratory and the Bayer Research Center in 1998, was established to establish insulin dependence by binding with the corresponding ligand to participate in receptor-mediated endocytosis. The full-length cDNA of the LRP5 gene was cloned by the Merck Laboratory and the Bayer Research Center in 1998. The LRP5 gene was isolated from the cDNA library of the liver by physical map of candidate region and transposable map. The LRP5 gene was isolated from the cDNA library of osteoblast when isolating the genes associated with osteoblast development. Studies have shown that LRP5 gene loss of functional mutations (including missense, Osteoporosis-Pseudoglioma Syndromesioma Syndromesioma OPSs, the main clinical manifestations of this syndrome are juvenile osteoporosis and pseudo glioma. It was also found that the bone mineral density of heterozygotes with LRP5 gene mutation was significantly lower than that of the control. Lrp5 knockout mice showed that homozygous mice were similar to human OPS phenotypes. Heterozygous mice showed obvious osteoporosis. On the other hand, the acquired functional mutation of LRP5 gene led to high bone mineral density. These results suggest that LRP5 gene plays an important role in bone mineral density regulation. LRP5 is widely present in human body. The surface of multi-tissue cells, Including liver, pancreas, small intestine, heart, lung, skeletal muscle, kidney, spleen, brain, peripheral blood cells, etc. Although LRP5 gene is expressed in many tissues, the phenotypic effect caused by gene mutation is limited to bone and eye. Other tissues and organs develop normally. At present, it is not clear about other aspects of the function of LRP5 gene, the mechanism of expression regulation and its role in the regulation of bone mineral density (BMD). It will be helpful to understand the function of LRP5 gene by clarifying the regulation mechanism of the gene expression.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R346

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