HETEROLOGOUS INTRONS CAN ENHANCE EXPRESSION OF TRANSGENES IN MICE

HETEROLOGOUS INTRONS CAN ENHANCE EXPRESSION OF TRANSGENES IN MICE
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DOI:
10.1073/pnas.88.2.478
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发表时间:
1991-01-01
影响因子:
11.1
通讯作者:
BRINSTER, RL
BRINSTER, RL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PALMITER, RD;SANDGREN, EP;BRINSTER, RL

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在先前的研究中,我们发现基因组构建体在转基因小鼠中的表达比除了缺少内含子之外完全相同的构建体更有效。 使用小鼠金属硫蛋白启动子-大鼠生长激素基因构建体作为模型,我们表明,大鼠生长激素基因的第一个内含子是高水平表达所必需的,而其他三个内含子是不太有效的。 位于无内含子大鼠生长激素基因编码区3'端的几个异源内含子也是无效的。 然而,在金属硫蛋白启动子和生长激素基因之间插入一些异源内含子可提高表达。 为了确定添加异源内含子是否会提供改善表达的一般策略,我们已经测试了它们与其他无内含子基因和不同的启动子。
In a previous study we showed that genomic constructs were expressed more efficiently in transgenic mice than constructs that were identical except for the lack of introns. Using the mouse metallothionein promoter-rat growth hormone gene construct as a model, we show that the first intron of the rat growth hormone gene is essential for high-level expression, whereas the other three introns are less effective. Several heterologous introns placed 3' of the coding region of an intronless rat growth hormone gene are also ineffective. However, insertion of some heterologous introns between the metallothionein promoter and the growth hormone gene improves expression. To determine whether addition of heterologous introns would provide a general strategy for improving expression, we have tested them in conjunction with other intronless genes and with different promoters.