Gene expression in scrapie -: Cloning a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts

Gene expression in scrapie -: Cloning a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts
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DOI:
10.1074/jbc.273.13.7691
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发表时间:
1998-03-27
影响因子:
4.8
通讯作者:
Dron, M
Dron, M
中科院分区:
生物学2区
文献类型:
--
作者:
Dandoy-Dron, F;Guillo, F;Dron, M

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为了确定与在传染性海绵状脑病中观察到的神经退行性变化相关或负责的基因,我们使用“mRNA差异显示”分析了羊瘙痒病感染小鼠脑中的基因表达。“在羊瘙痒病感染动物的大脑中,八个基因的RNA转录物增加了3-8倍,其中五个基因以前没有报道过在这种疾病中表现出表达增加:组织蛋白酶S、补体的C1 q B链、载脂蛋白D和两个先前未鉴定的命名为羊瘙痒症应答基因(ScRG)-1和ScRG-2的基因,其优先在脑组织中表达,先前已报道在实验性羊瘙痒症中发生其余三种基因β 2微球蛋白、F4/80和金属硫蛋白II的表达增加。动力学分析显示ScRG-1、组织蛋白酶S、补体的C1 q B链和β 2微球蛋白mRNA以及神经胶质细胞酸性蛋白和F4/80转录物的水平伴随增加,相反,ScRG-2、载脂蛋白D和金属硫蛋白II mRNA的水平仅在疾病的终末期增加。发现ScRG-1 mRNA优先在神经胶质细胞中表达,并编码具有强疏水性N-末端区域的47个氨基酸的短蛋白。
To define genes associated with or responsible for the neurodegenerative changes observed in transmissible spongiform encephalopathies, we analyzed gene expression in scrapie-infected mouse brain using "mRNA differential display." The RNA transcripts of eight genes were increased 3-8-fold in the brains of scrapie-infected animals, Five of these genes have not previously been reported to exhibit increased expression in this disease: cathepsin S, the C1q B-chain of complement, apolipoprotein D, and two previously unidentified genes denominated scrapie-responsive gene (ScRG)-1 and ScRG-2, which are preferentially expressed in brain tissue, Increased expression of the three remaining genes, beta 2 microglobulin, F4/80, and metallothionein II, has previously been reported to occur in experimental scrapie, Kinetic analysis revealed a concomitant increase in the levels of ScRG-1, cathepsin S, the C1q B-chain of complement, and beta 2 microglobulin mRNA as well as glial fibrillary acidic protein and F4/80 transcripts, markers of astrocytosis and microglial activation, respectively, In contrast, the level of ScRG-2, apolipoprotein D, and metallothionein II mRNA was only increased at the terminal stage of the disease. ScRG-1 mRNA was found to be preferentially expressed in glial cells and to code for a short protein of 47 amino acids with a strong hydrophobic N-terminal region.