LAC REPRESSOR MOUSE

lac Repressor鼠标是系统的关键和最终组件， 调节小鼠中的基因表达，其基于 E.杆菌 该项目的长期目标是使 生物医学界的资源，这将使它有可能， 将条件致死突变引入哺乳动物基因组， 在生物体的背景下分析它们的表型后果 与人类密切相关。 就像利用温度 敏感的突变来研究细菌中的致命突变， 真核生物，该系统将允许th引入和分析 胚胎致死基因在生物体水平上，而不损害 宿主的生存能力。 老鼠体内乳糖系统的雏形相对简单， 产生表达功能性lac的阻遏小鼠系 抑制子;以及，对预期的启动子区域的修饰。 转基因或内源基因座，使得其含有用于以下的DNA结合位点 Lac操作符（Lac Operator） 转移到lac Repressor小鼠中 在背景中，这样的启动子变得对阻遏物的调节敏感， 表达的那些组织。 本项目的具体目标 集中于获取关于何时以及在哪些组织中的信息 蛋白质可以被检测到，更重要的是，它的功能如何， 在组织和生物体水平上调节基因表达。 等 实验将在纯合紫胶的两个单独的品系上进行 已经证明抑制基因转基因的抑制小鼠 转录活性。 如所附申请中所述， 使用来自以下的调节元件调节整个动物中的基因表达： E.大肠杆菌即将成功。 理论上，这 技术将扩大人类疾病的表型复制的可能性， eh小鼠包括有害的，功能丧失的突变， 到目前为止还无法进行实验操作的基因。

The lac Repressor mouse is the key and final component of a system for regulating gene expression in the mouse that is based on the lac operon of E. coli. The long-term goal of this project is to make available to the biomedical community at large a resource that will make it possible to introduce conditional lethal mutations into the mammalian genome and to analyze their phenotypic consequences within the context of an organism closely related to the human. Like analogous systems that use temperature sensitive mutations to study lethal mutations in bacteria and lower eukaryotes, this system would allow th introduction and analysis of embryonic lethal genes at the organismal level without compromising the viability of their host. The rudiments of the lac system ina the mouse are relatively simple; the creation of a line of Repressor mouse that expresses functional lac Repressor; and, modifications of the promoter region of a prospective transgene or endogenous locus so that it contains the DNA binding site for the Repressor (the lac operator). Transferred into a lac Repressor mouse background, such promoters become sensitive to regulation by Repressor in those tissues in which it is expressed. The Specific Aims of this project focus on acquiring information about when and in which tissues Repressor protein can be detected, and, more importantly, how well it functions to regulate gene expression at both the tissue and organismal levels. Such experiments will be carried out on two individual lines of homozygous lac Repressor mice in which Repressor transgenes have already been shown to be transcriptionally active. As described in the enclosed application, the technology required to regulate gene expression in the whole animal using regulatory elements from the lac operon of E. coli is on the verge of success. Theoretically, this technology would extend the possibilities of phenocopying human disease int eh mouse to include deleterious, loss-of-function mutations in essential genes that up to now have been inaccessible to experimental manipulation.