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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DISCOVERY OF A BRAIN PROMOTER FROM THE HUMAN TRANSFERRIN GENE AND ITS UTILIZATION FOR DEVELOPMENT OF TRANSGENIC MICE THAT EXPRESS HUMAN APOLIPOPROTEIN E ALLELES
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DISCOVERY OF A BRAIN PROMOTER FROM THE HUMAN TRANSFERRIN GENE AND ITS UTILIZATION FOR DEVELOPMENT OF TRANSGENIC MICE THAT EXPRESS HUMAN APOLIPOPROTEIN E ALLELES

机译：人转铁蛋白基因中脑启动子的发现及其在表达人类载脂蛋白E等位基因的转基因小鼠中的应用

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Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain, Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein, In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain, High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes, Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains, The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains, The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.
机译：携带由人转铁蛋白（TF）基因调​​节序列的670-bp片段定向的异源基因的转基因小鼠在脑中显示出高表达，携带嵌合0.67kbTF-CAT基因的小鼠在其神经元和神经胶质细胞中表达了TF-CAT。基底核，大脑，call体，小脑和海马体。在两个独立的TF-CAT转基因创建者系的大脑中，TF-CAT mRNA的拷贝数超过了编码小鼠内源性转铁蛋白或小鼠内源性淀粉样前体蛋白的mRNA转录物的数量。在两个转基因创建者系中，氯霉素乙酰基转移酶（CAT）蛋白由TF-CAT mRNA合成的蛋白估计占大脑总可溶性蛋白的0.10-0.15％，在大脑中观察到的高表达表明0.67kbTF启动子是异源基因在大脑中表达的有希望的指导者，因此，该启动子已被用于在转基因小鼠大脑中表达三种常见的人类载脂蛋白E（apoE）等位基因。该apoE等位基因与阿尔茨海默氏病的表达有关，据报道，人类apoE亚型与大脑的β-亲和力具有不同的亲和力淀粉样蛋白和tau蛋白在体外。这项研究的结果证明了人类apoE蛋白在转基因小鼠大脑中的高表达和生产。该模型可用于表征人类apoE同工型与其他脑蛋白的相互作用，并提供有助于设计阿尔茨海默病治疗策略的信息。

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