Expression of APP in transgenic mice: A comparison of neuron-specific promoters
Expression of APP in transgenic mice: A comparison of neuron-specific promoters
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DOI：
10.1016/0197-4580(95)02066-7
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发表时间：
1996-03-01
影响因子：
4.2
通讯作者：
Staufenbiel, M
中科院分区：
文献类型：
--
作者：
Andra, K;Abramowski, D;Staufenbiel, M
β -淀粉样蛋白前体蛋白（APP）携带717或670/671密码子突变，与家族性阿尔茨海默病（AD）共分离。作为在体内研究相关发病机制的第一步，我们培育了带有这些突变的表达APP的转基因小鼠。几个神经元特异性启动子被用来驱动人类APP cdna的表达。只有Thy-1启动子产生了与内源性小鼠水平相当或更高的转基因表达水平。从APP的3'非翻译区删除一个121 bp的序列似乎增加了mRNA水平。转基因mRNA遍布全脑，海马和大脑皮层表达量最高。相应的;Western blotting在这些区域检测人类APP。蛋白质水平与mRNA水平平行，达到或超过内源性APP的量。免疫细胞化学显示人APP在细胞体中的可变反应性。虽然我们最初的组织学检查没有发现AD的任何改变特征，但需要进一步的研究。
The beta-amyloid precursor protein (APP) carries mutations in codons 717 or 670/671, which cosegregate with familial forms of Alzheimer's disease (AD). As an initial step to study the related pathogenetic mechanisms in vivo we have generated transgenic mice expressing APP with these mutations. Several neuron-specific promoters were used to drive expression of human APP cDNAs. Only the Thy-1 promoter yielded transgene expression levels comparable to or above the endogenous mouse levels. Deletion of a 121 bp sequence from the 3' untranslated region of APP appeared to increase mRNA levels. Transgene mRNA was found throughout the brain with highest levels in hippocampus and cerebral cortex. Accordingly; human APP was detected in these regions by Western blotting. Protein levels paralleled mRNA levels reaching or exceeding the amount of endogenous APP. Variable reactivity of human APP in cell bodies was shown by immunocytochemistry. Although our initial histological examinations did not reveal any alterations characteristic of AD, further studied will be required.