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首页> 外文期刊>Molecular and Cellular Biology >Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3.
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Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3.

机译：分析包含β-珠蛋白基因座控制区5'超敏位点3的靶点缺失的小鼠。

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摘要

To examine the function of murine beta-globin locus region (LCR) 5' hypersensitive site 3 (HS3) in its native chromosomal context, we deleted this site from the mouse germ line by using homologous recombination techniques. Previous experiments with human 5' HS3 in transgenic models suggested that this site independently contains at least 50% of total LCR activity and that it interacts preferentially with the human gamma-globin genes in embryonic erythroid cells. However, in this study, we demonstrate that deletion of murine 5' HS3 reduces expression of the linked embryonic epsilon y- and beta H 1-globin genes only minimally in yolk sac-derived erythroid cells and reduces output of the linked adult beta (beta major plus beta minor) globin genes by approximately 30% in adult erythrocytes. When the selectable marker PGK-neo cassette was left within the HS3 region of the LCR, a much more severe phenotype was observed at all developmental stages, suggesting that PGK-neo interferes with LCR activity when it is retained within the LCR. Collectively, these results suggest that murine 5' HS3 is not required for globin gene switching; importantly, however, it is required for approximately 30% of the total LCR activity associated with adult beta-globin gene expression in adult erythrocytes.
机译：若要检查其天然染色体上下文中的鼠β-珠蛋白基因座区域（LCR）5'超敏位点3（HS3）的功能，我们通过使用同源重组技术从小鼠种系中删除了该位点。先前在转基因模型中使用人5'HS3进行的实验表明，该位点独立包含至少50％的总LCR​​活性，并且它优先与胚胎红系细胞中的人γ-珠蛋白基因相互作用。但是，在这项研究中，我们证明删除鼠5'HS3只能在卵黄囊来源的类红细胞中最小程度地减少链接的胚胎ε和βH 1珠蛋白基因的表达，并减少链接的成年β（β成年红细胞中约30％的主要基因（加上β次要基因）珠蛋白基因）。当选择标记PGK-neo序列盒是在LCR的HS3区域内留在所有发育阶段，观察到更严重的表型，这表明与LCR活性PGK-neo中干涉当它在LCR中保留。总的来说，这些结果表明鼠5'HS3不是球蛋白基因转换所必需的。然而重要的是，与成人红细胞中成人β-珠蛋白基因表达相关的总LCR​​活性约为30％。

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