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利用小鼠作为实验模型来研究糖尿病研究中的基础和临床相关问题的能力。转基因和敲除小鼠核心(TKMC，Core A)为加州大学洛杉矶分校、加州大学圣地亚哥分校、索尔克研究所和锡达斯-西奈大学的研究人员提供了一系列在小鼠中进行的遗传操作，包括转基因基因、胚胎干细胞(ES细胞)的同源重组、从ES细胞创建嵌合体小鼠，以及在小鼠中进行反向遗传学的最尖端方法。转基因、敲除和敲入小鼠模型的建立利用了最先进的方法，包括条件Tet诱导和他莫昔芬诱导的转基因，使用Cre-loxP和FLP重组酶的组织特异性和条件敲除和重组介导盒交换(RMCE)，BAC转基因，BAC-Trap，RiboTag和其他专门技术。这个核心是一个杰出的例子，说明了不能合理地期望在个人基础上开发这些技术的研究人员如何能够使用非凡的专门技术、训练有素的专门人员、专门建造的设施和昂贵的设备。 主要目标是： 1.为糖尿病及其并发症的研究创造创新的重要小鼠模型 2.为DERC成员消除最尖端的小鼠遗传方法的障碍 3.提供卓越、可靠、高质量的小鼠胚胎和遗传服务 4.推进小鼠基因组遗传操作技术 这一转基因和敲除小鼠核心与代谢和分子生理学核心、基因组学和表观遗传核心以及新的靶标识别和分析开发核心相结合，将使我们的成员能够利用一系列多学科、最先进的技术在小鼠中进行多功能、尖端和反向遗传学研究。

It is clear that the progress of diabetes research during the coming decade will depend heavily upon the ability to utilize the mouse as an experimental model to investigate both basic and clinically relevant questions in diabetes research. The Transgenic and Knock-out Mouse Core (TKMC, Core A) provides investigators at UCLA, UCSD, the Salk Institute, and Cedars-Sinai with a wide array of genetic manipulations in the mouse including transgenic genes, homologous recombination in embryonic stem cells (ES cells), creation of chimeric mice from ES cells, and the most cutting-edge approaches to performing reverse genetics in the mouse. Transgenic, knock-out and knock-in mouse models are created that utilize the most advanced approaches including conditional Tet-inducible and tamoxifen-inducible transgenes, tissue-specific and conditional knock-outs using Cre-LoxP and Flp recombinases and recombination-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 complications 2. To eliminate barriers to the most cutting-edge mouse genetic approaches for the DERC membership 3. To provide outstanding, reliable, and high quality mouse embryology and genetic services 4. To advance the technology of genetic manipulation of the mouse genome The availability of this Transgenic and Knock-out Mouse Core in coordination with the Metabolic and Molecular Physiology Core, the Genomics and Epigenetic Core, and the Novel Target identification and Assay Development Core, will enable our members to conduct versatile, cutting-edge, reverse genetic research in the mouse with a battery of multidisciplinary, state-of-the-art techniques.