本文關(guān)鍵詞： LDL受體相關(guān)蛋白5 LRP5基因 基因表達(dá)調(diào)控 啟動(dòng)子 轉(zhuǎn)錄因子 熒光素酶報(bào)告基因分析系統(tǒng)　出處：《山東大學(xué)》2005年博士論文　論文類型：學(xué)位論文

【摘要】：低密度脂蛋白受體相關(guān)蛋白5(low densjty lipoprotein receptor re]ated protein5,LRP5)是細(xì)胞表面的受體蛋白,屬于低密度脂蛋白受體家族,可通過(guò)與相應(yīng)配體結(jié)合參與受體介導(dǎo)的細(xì)胞內(nèi)吞作用而實(shí)現(xiàn)多方面的功能。LRP5基因全長(zhǎng)cDNA是1998年分別由Merck實(shí)驗(yàn)室和Bayer研究中心克隆的。Merck實(shí)驗(yàn)室是在建立胰島素依賴性糖尿病基因候選區(qū)域物理圖和轉(zhuǎn)錄圖時(shí)從肝臟的cDNA文庫(kù)中分離得到LRP5基因的。Bayer實(shí)驗(yàn)室是在分離成骨細(xì)胞發(fā)育相關(guān)基因時(shí)從成骨細(xì)胞cDNA文庫(kù)中分離到該基因的。研究標(biāo)明LRP5基因喪失功能突變(包括錯(cuò)義,無(wú)義及移碼突變)導(dǎo)致骨質(zhì)疏松-假性神經(jīng)膠質(zhì)瘤綜合征(Osteoporosis-Pseudoglioma Syndrome,OPS),該綜合征的主要臨床表現(xiàn)為幼年型骨質(zhì)疏松和假性神經(jīng)膠質(zhì)瘤,并發(fā)現(xiàn)攜帶LRP5基因突變的雜合子骨密度顯著低于對(duì)照組。Lrp5基因敲除小鼠分析表明,純合子小鼠表現(xiàn)為類似于人類OPS表型,雜合子小鼠表現(xiàn)為明顯的骨質(zhì)疏松。另一方面,LRP5基因的獲得功能突變導(dǎo)致高骨密度癥。這些結(jié)果提示LRP5基因在骨密度調(diào)節(jié)過(guò)程中起重要作用。LRP5廣泛存在于人體許多組織細(xì)胞表面,包括肝、胰、小腸、心、肺、骨骼肌、腎、脾、腦、外周血細(xì)胞等。盡管LRP5基因在多種組織中表達(dá),但基因突變所引起的表型效應(yīng)僅局限在骨骼和眼,其它組織器官發(fā)育正常。目前關(guān)于LRP5基因的其它方面功能、表達(dá)調(diào)控機(jī)制以及其在骨密度調(diào)節(jié)過(guò)程中的作用機(jī)制尚不清楚,闡明該基因表達(dá)的調(diào)控機(jī)制將有助于理解LRP5基因的功能。為此,本課題進(jìn)行了以下幾個(gè)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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R346

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 呂萍,龔瑤琴,李江夏,周海斌,陳丙璽;小鼠Lrp5基因基本啟動(dòng)子分析[J];山東大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2004年04期

2 呂萍,龔瑤琴,李江夏,周海斌,陳丙璽;小鼠Lrp5基因啟動(dòng)子的克隆及功能分析[J];中國(guó)生物化學(xué)與分子生物學(xué)報(bào);2005年01期

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本文編號(hào)：1526862