Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice.
Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice.
复制标题
转基因小鼠中酵母人工染色体中人类 β-淀粉样蛋白前体蛋白基因的表达。
DOI：
10.1073/pnas.90.22.10578
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发表时间：
1993
影响因子：
11.1
通讯作者：
Choi,TK
中科院分区：
文献类型：
--
作者：
Pearson,BE;Choi,TK
阿尔茨海默病的一个标志是在大脑中形成淀粉样斑块，该淀粉样斑块含有源自β-淀粉样前体蛋白（APP）的小肽。APP基因在外周组织和脑中表现出复杂的表达模式。通过共脂质转染650 kb酵母人工染色体（YAC）将整个人APP基因导入胚胎干（ES）细胞。分离出含有基本上完整的YAC的三个ES系，并且获得了与内源性小鼠APP转录物的水平相当的人APP mRNA的表达。通过APP YAC的种系传递建立转基因小鼠系。人APP mRNA的RNA酶保护分析证明了ES细胞和转基因动物脑中初级APP转录物的适当剪接。这些小鼠可能有助于阐明体内各种APP亚型的功能。
One hallmark of Alzheimer disease is the formation in the brain of amyloid plaques containing a small peptide derived from the beta-amyloid precursor protein (APP). The APP gene exhibits a complex pattern of expression in peripheral tissues and in the brain. The entire human APP gene was introduced into embryonic stem (ES) cells by co-lipofection of a 650-kb yeast artificial chromosome (YAC). Three ES lines containing an essentially intact YAC were isolated, and expression of human APP mRNAs at levels comparable to those of endogenous mouse APP transcripts was obtained. A transgenic mouse line was established by germ-line transmission of the APP YAC. RNase protection analysis of human APP mRNAs demonstrated appropriate splicing of the primary APP transcript in ES cells and in the brain of a transgenic animal. These mice may be useful for elucidating the function of the various APP isoforms in vivo.