COBRE: UNR: TARGETED & TRANSGENIC ANIMAL CORE (A): ES CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 内华达转基因中心是内华达州第一家也是唯一一家老鼠转基因设施。这一核心的目标是让没有接受过哺乳动物胚胎操作、胚胎干细胞培养、动物育种或显微注射技术细节培训的研究人员获得转基因技术。内华达州转基因中心已成功培育出缺乏氯离子通道ClC-3、α7整合素链和睾丸特异Bax样蛋白BAT1的小鼠。此外，还产生了在心脏过度表达氯离子通道ClC-3的长和短异构体的小鼠。为ClC-3和钾离子通道TREK1产生组织特异性(cre/lox)或可诱导(四环素)基因敲除小鼠的技术目前正在转基因Core中使用。转基因核心由三个部分组成。首先，胚胎干细胞设施提供完整的小鼠胚胎干细胞培养和基因打靶服务。其次，显微注射设备进行原核和囊胚注射。第三，动物服务机构为核心研究人员提供小鼠和胚胎，进行胚胎移植，并负责管理转基因小鼠品系和群体。此外，核心人员还监督Cobre研究人员使用的转基因小鼠的育种计划。在下一个资助期，Cobre研究人员转基因核心将产生过表达或缺乏心脏氯通道(如ClC-2、Bestrophin)、心脏整合素链(Beta1和Alpha7整合素)和调节蛋白(活化C激酶受体(RACK1)和血清/糖皮质激素调节激酶(SGK))的小鼠。这些转基因小鼠的产生将提供宝贵的资源，使Cobre研究人员能够继续研究氯通道活动改变对心脏功能的病理生理学后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Nevada Transgenic Center is the first and only mouse transgenic facility in the state of Nevada. The objective of this Core is to make transgenic technology available to investigators who are not trained in the technical details of mammalian embryo manipulation, embryonic stem cell culture, animal breeding or microinjection. The Nevada Transgenic Center has successfully produced mice lacking the chloride ion channel ClC-3, alpha7 integrin chain and testis specific Bax-like protein, BAT1. In addition, mice over-expressing the long and short isoforms of the chloride ion channel ClC-3 in the heart have been produced. Technology to generate tissue-specific (cre/lox) or inducible (tetracycline) knockout mice for ClC-3 and the potassium ion channel TREK1 are currently being employed within the Transgenic Core. The Transgenic Core consists of three components. First, an embryonic stem cell facility provides a complete mouse embryonic stem cell culture and gene targeting services. Second, a microinjection facility performs pronuclear and blastocyst injections. Third, an animal service provides mice and embryos for the core researchers, performs embryo transfers, and has the responsibility for managing transgenic mouse lines and colonies. In addition, core personnel oversee breeding programs for transgenic mice used by COBRE investigators. In this next funding period, mice over-expressing or lacking cardiac chloride channels (e.g. ClC-2, Bestrophin), cardiac integrin chains (beta1 and alpha7 integrin) and regulatory proteins (Receptor for Activated C Kinase (RACK1) and Serum/Glucocorticoid regulated Kinase (SGK)) will be generated by the Transgenic Core for COBRE investigators. Generation of these genetically modified mice will provide a valuable resource to allow COBRE investigators to continue to study the pathophysiological consequences of altered chloride channel activity on cardiac function.