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首页> 外文期刊>Molecular and Cellular Biology >Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice.
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Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice.

机译：小鼠金属硫蛋白基因座的远端调控元件刺激转基因小鼠中的基因表达。

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摘要

DNA regions of 10 and 7 kb that flank the mouse metallothionein II (MT-II) and MT-I genes, respectively, were combined with a minimally marked MT-I (MT-I*) gene and tested in transgenic mice. This construct resulted in (i) position-independent expression of MT-I* mRNA and copy number-dependent expression, (ii) levels of hepatic MT-I mRNA per cell per transgene that were about half that derived from endogenous MT-I genes, (iii) appropriate regulation by metals and hormones, and (iv) tissue distribution of transgene mRNA that resembled that of endogenous MT-I mRNA. These features were not observed when MT-I* was tested without the flanking regions. These MT-I flanking sequences also improved the expression of rat growth hormone reporter genes, with or without introns, that were under the control of the MT-I promoter. Moreover, they enhanced expression from two of four heterologous promoters/enhancers that were tested. Deletion analysis indicated that regions known to have DNase I-hypersensitive sites were necessary but not sufficient for high-level expression. These data suggest that the DNA regions flanking the mouse MT-I and MT-II genes have functions like the locus control regions described for other genes.
机译：将分别位于小鼠金属硫蛋白II（MT-II）和MT-1基因两侧的10和7 kb DNA区域与最低限度标记的MT-1（MT-1）基因结合，并在转基因小鼠中进行测试。该构建体导致（i）MT-1 * mRNA的位置依赖性表达和拷贝数依赖性表达;（ii）每个转基因每个细胞的肝MT-1 mRNA水平约为内源MT-1基因的一半，（iii）金属和激素的适当调节，以及（iv）与内源MT-1 mRNA类似的转基因mRNA的组织分布。当测试没有侧翼区域的MT-1 *时，未观察到这些特征。这些MT-1侧翼序列还改善了受MT-1启动子控制的有或没有内含子的大鼠生长激素报告基因的表达。而且，它们增强了来自所测试的四个异源启动子/增强子中两个的表达。缺失分析表明，已知具有DNase I超敏位点的区域是必需的，但不足以进行高水平表达。这些数据表明，小鼠MT-1和MT-II基因侧翼的DNA区域具有类似于其他基因所描述的基因座控制区域的功能。

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