Regulation of the human apolipoprotein AIV gene expression in transgenic mice
Regulation of the human apolipoprotein AIV gene expression in transgenic mice
复制标题
DOI：
10.1016/s0014-5793(99)00096-4
复制
发表时间：
1999-02-19
期刊：
影响因子：
3.5
通讯作者：
Ochoa, A
中科院分区：
文献类型：
--
作者：
Baralle, M;Vergnes, L;Ochoa, A
载脂蛋白 (Apo) AI-CIII-AIV 基因簇具有复杂的基因表达模式，受基因和簇特异性顺式作用元件的调节。特别是，Apo AIV 表达的调节先前已在体内和体外进行过研究，包括几种转基因驼鹿系，但仍然缺乏组织特异性对照的完整、一致的图片。我们使用体外和体内系统（包括三系转基因小鼠）分析了 Apo AIV 3' 侧翼序列在基因表达调节中的作用。该转基因由含有 7 kb 5' 侧翼区域、Apo AIV 基因本身和 6 kb 3' 侧翼区域 (-7+6 Apo ATV) 的人片段组成。使用定量 PCR 和 Northern 印迹对 Apo AIV mRNA 水平进行准确分析表明，-7+6 kb Apo AIV 片段赋予肝脏特异性调节，因为人 Apo AIV 转基因的表达水平与人 Apo AIV 转基因的表达水平大致相同。内源性小鼠 Apo AIV 基因。相反，转基因的肠道调节并不遵循内源基因观察到的模式，尽管它按照公认的人类模式产生了更高的肠道表达。因此，该动物模型为设计代谢紊乱的治疗方案提供了极好的基础，这些代谢紊乱可能受益于 Apo AIV 水平的变化及其抗动脉粥样硬化作用。 (C) 1999 年欧洲生化学会联合会。
The apolipoprotein (Apo) AI-CIII-AIV gene cluster has a complex pattern of gene expression that is modulated by both gene- and cluster-specific cis-acting elements. In particular the regulation of Apo AIV expression has been previously studied in vivo and in vitro including several transgenic moose lines but a complete, consistent picture of the tissue-specific controls is still missing. We have analysed the role of the Apo AIV 3' flanking sequences in the regulation of gene expression using both in vitro and in vivo systems including three lines of transgenic mice. The transgene consisted of a human fragment containing 7 kb of the 5' flanking region, the Apo AIV gene itself and 6 kb of the 3' flanking region (-7+6 Apo ATV), Accurate analysis of the Apo AIV mRNA levels using quantitative PCR and Northern blots showed that the -7+6 kb Apo AIV fragment confers liver-specific regulation in that the human Apo AIV transgene is expressed at approximately the same level as the endogenous mouse Apo AIV gene. In contrast, the intestinal regulation of the transgene did not follow the pattern observed with the endogenous gene although it produced a much higher intestinal expression following the accepted human pattern. Therefore, this animal model provides an excellent substrate to design therapeutic protocols for those metabolic derangements that may benefit from variations in Apo AIV levels and its anti-atherogenic effect. (C) 1999 Federation of European Biochemical Societies.