CORE A: TRANSGENIC AND KNOCKOUT MOUSE CORE

很明显，未来十年糖尿病研究的进展将在很大程度上取决于 能够将小鼠用作实验模型，以研究基础和临床相关 糖尿病研究中的问题。转基因和敲除小鼠核心（TKMC，核心A）提供了 加州大学洛杉矶分校，加州大学圣地亚哥分校，索尔克研究所和雪松西奈半岛的研究人员进行了广泛的基因操作 在小鼠中包括转基因，在胚胎干细胞（ES细胞）中同源重组， 从胚胎干细胞创造嵌合小鼠，以及最先进的方法来执行逆转录病毒， 老鼠的基因转基因，敲除和敲入小鼠模型的建立，利用最多的 先进的方法，包括条件性Tet-inducible和tamoxifen-inducible转基因，裂缝特异性 以及使用Cre-LoxP和Flp重组酶和重组介导的盒的条件性敲除 交换（RMCE）、BAC转基因、BAC陷阱、RiboTag和其他专门技术。该芯 这是一个杰出的例子，说明了如何非常专业的技术，训练有素的敬业人员， 专门建造的设施和昂贵的设备可以由研究人员谁不能访问 合理地期望在个人基础上发展它们。 主要目标是： 1.为糖尿病及其并发症的研究创建创新且重要的小鼠模型 2.为DERC成员消除最前沿的小鼠遗传学方法的障碍 3.提供优秀、可靠、高质量的小鼠胚胎学和遗传学服务 4.促进小鼠基因组的遗传操作技术 这种转基因和敲除小鼠核心与代谢和免疫调节系统协调的可用性。 分子生理学核心，基因组学和表观遗传学核心，以及新的靶向治疗和 分析开发核心，将使我们的成员进行重复文件，尖端，反向遗传学 用一系列多学科的、最先进的技术在老鼠身上进行研究。

It is clear that the progress of diabetes research during the coming decade will depend heavily upon the ability to ufilize the mouse as an experimental model to invesfigate both basic and clinically relevant quesfions in diabetes research. The Transgenic and Knock-out Mouse Core (TKMC, Core A) provides invesfigators at UCLA, UCSD, the Salk Institute, and Cedars-Sinai with a wide array of genefic manipulafions in the mouse including transgenic genes, homologous recombinafion in embryonic stem cells (ES cells), creation of chimeric mice from ES cells, and the most cutting-edge approaches to performing reverse genefics in the mouse. Transgenic, knock-out and knock-in mouse models are created that utilize the most advanced approaches including condifional Tet-inducible and tamoxifen-inducible transgenes, fissue-specific and condifional knock-outs using Cre-LoxP and Flp recombinases and recombinafion-mediated cassette exchange (RMCE), BAC transgenics, BAC-Trap, RiboTag, and other specialized technologies. This Core is an outstanding example of how extraordinarily specialized techniques, highly trained dedicated personnel, specially constructed facilities, and expensive equipment can be accessed by researchers who could not reasonably expect to develop them on an individual basis. Key objectives are: 1. To create innovative and important mouse models for studies of diabetes and its complicafions 2. To eliminate barriers to the most cutfing-edge mouse genefic approaches for the DERC membership 3. To provide outstanding, reliable, and high quality mouse embryology and genefic services 4. To advance the technology of genefic manipulafion of the mouse genome The availability of this Transgenic and Knock-out Mouse Core in coordinafion with the Metabolic and Molecular Physiology Core, the Genomics and Epigenefics Core, and the Novel Target idenfificafion and Assay Development Core, will enable our members to conduct versafile, cutting-edge, reverse genefic research in the mouse with a battery of multidisciplinary, state-of-the-art techniques.