Development of a unique system for spatiotemporal and lineage-specific gene expression in mice
Development of a unique system for spatiotemporal and lineage-specific gene expression in mice
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DOI：
10.1073/pnas.0500124102
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发表时间：
2005-06-14
影响因子：
11.1
通讯作者：
Hsu, W
中科院分区：
文献类型：
--
作者：
Yu, HMI;Liu, B;Hsu, W
我们开发了一种先进的方法，将Cre介导的表达系统和四环素依赖的表达系统整合在一起，在小鼠中进行条件基因表达。将rtA基因插入到rosa26基因座，建立了R26STOPrtTA小鼠品系。当终止序列被Cre介导的重组切除时，RTTA在表达Cre的细胞及其所有衍生物中表达。因此，RTTA的细胞类型、组织或谱系特异性的表达是通过使用适当的Cre转基因菌株来实现的。在同样携带受四环素反应元件控制的靶基因的小鼠中，靶基因的可诱导表达受到给予多西环素的时间调节。我们的结果表明，这个通用的系统是唯一适合时空和谱系特异的基因表达的诱导方式。基因表达可以在特定的细胞类型和谱系中进行操纵，具有传统方法难以实现的灵活性。
We have developed an advanced method for conditional gene expression in mice that integrates the Cre-mediated and tetracycline-dependent expression systems. An rtTA gene, preceded by a loxP-flanked STOP sequence, was inserted into the ROSA26 locus to create a R26STOPrtTA mouse strain. When the STOP sequence is excised by Cre-mediated recombination, the rtTA is expressed in the Cre-expressing cells and all of their derivatives. Therefore, cell type-, tissue-, or lineage-specific expression of rtTA is achieved by the use of an appropriate Cre transgenic strain. In mice also carrying a target gene under the control of the tetracycline response element, inducible expression of the target gene is temporally regulated by administration of doxycycline. Our results demonstrate that this universal system is uniquely suited for spatiotemporal and lineage-specific gene expression in an inducible fashion. Gene expression can be manipulated in specific cell types and lineages with a flexibility that is difficult to achieve with conventional methods.