Regulatory region of human amyloid precursor protein (APP) gene promotes neuron‐specific gene expression in the CNS of transgenic mice.
Regulatory region of human amyloid precursor protein (APP) gene promotes neuron‐specific gene expression in the CNS of transgenic mice.
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人类淀粉样前体蛋白（APP）基因的调节区促进转基因小鼠中枢神经系统中神经元特异性基因的表达。
DOI：
10.1002/j.1460-2075.1991.tb07949.x
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
A. Unterbeck
中科院分区：
文献类型：
--
作者：
Dana O. Wirak;Richard M. Bayney;Catherine A.kundel;Alice S. Lee;George Scangos;Bruce D. Trapp;A. Unterbeck
β-淀粉样蛋白在特定脑区的积累是阿尔茨海默病（AD）的主要病理特征。4 kd β-淀粉样蛋白是由一种更大的淀粉样前体蛋白（APP）通过未知的机制衍生而来的。在缺乏AD实验室动物模型的情况下，表达各种APP基因产物的转基因小鼠可能为APP和β淀粉样蛋白形成与AD发病机制之间的关系提供新的见解。AD脑中的β淀粉样蛋白积聚可能是APP与其他分子之间相互作用的结果。这种相互作用可能是发育调节和组织特异性的。因此，AD的转基因小鼠模型旨在模拟内源性APP基因的APP转基因表达。作为开发动物模型的第一步，我们已经从人APP基因的5′端鉴定了一个4.5 kb的DNA片段，该片段介导转基因小鼠CNS中神经元特异性基因表达，使用E. colilacZ作为报告基因。在大多数神经元中发现可检测水平的转基因表达，但在神经胶质细胞和血管内皮细胞中没有。该报告基因的表达模式与人和小鼠CNS中内源性APP mRNA的分布非常相似。
The accumulation of beta‐amyloid protein in specific brain regions is a central pathological feature of Alzheimer's disease (AD). The 4 kd beta‐amyloid protein derives from a larger amyloid precursor protein (APP) by as yet unknown mechanisms. In the absence of a laboratory animal model of AD, transgenic mice expressing various APP gene products may provide new insights into the relationship between APP and beta‐amyloid formation and the pathogenesis of AD. beta‐amyloid accumulation in AD brain may result from interactions between APP and other molecules. Such interactions are likely to be developmentally regulated and tissue‐specific. A transgenic mouse model of AD, therefore, would aim for APP transgene expression that mimics the endogenous APP gene. As an initial step in developing an animal model, we have identified a 4.5 kb DNA fragment from the 5′ end of the human APP gene, which mediates neuron‐specific gene expression in the CNS of transgenic mice, using E. coli lacZ as a reporter gene. Detectable levels of transgene expression are found in most neurons but not in glial and vascular endothelial cells. The expression pattern of this reporter gene closely resembles the distribution of endogenous APP mRNA in both the human and mouse CNS.