INTRODUCTION AND EXPRESSION OF THE 400 KILOBASE PRECURSOR AMYLOID PROTEIN GENE IN TRANSGENIC MICE
INTRODUCTION AND EXPRESSION OF THE 400 KILOBASE PRECURSOR AMYLOID PROTEIN GENE IN TRANSGENIC MICE
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DOI：
10.1038/ng0993-22
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发表时间：
1993-09-01
期刊：
影响因子：
30.8
通讯作者：
GEARHART, JD
中科院分区：
文献类型：
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作者：
LAMB, BT;SISODIA, SS;GEARHART, JD
编码β -淀粉样前体蛋白（APP）的基因过度表达可能在阿尔茨海默病（AD）和唐氏综合征（DS）的发病机制中起关键作用。因此，我们通过脂质介导的转染方法，将一个含有完整的、未重排的400kb人类APP基因的650千碱基（kb）酵母人工染色体（YAC）导入小鼠胚胎干细胞（ES）中。我们获得了含有稳定整合的、未重排的人类APP基因的ES细胞系。此外，我们证明了APP YAC在转基因小鼠中的生殖系传递，以及人类APP mRNA和蛋白质的表达水平与内源性APP相当。这种转基因策略可能对开发阿尔茨海默病和唐氏综合征的小鼠模型具有极其重要的价值。
Overexpression of the gene encoding the beta-amyloid precursor protein (APP) may have a key role in the pathogenesis of both Alzheimer's disease (AD) and Down Syndrome (DS). We have therefore introduced a 650 kilobase (kb) yeast artificial chromosome (YAC) that contains the entire, unrearranged 400 kb human APP gene into mouse embryonic stem (ES) cells by lipid-mediated transfection. ES lines were generated that contain a stably integrated, unrearranged human APP gene. Moreover, we demonstrate germ line transmission of the APP YAC in transgenic mice and expression of human APP mRNA and protein at levels comparable to endogenous APP. This transgenic strategy may prove invaluable for the development of mouse models for AD and DS.