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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 内华达州转基因中心是内华达州第一个也是唯一一个转基因小鼠设施。该核心的目的是使转基因技术可用于未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。内华达州转基因中心已经成功地生产出缺乏氯离子通道ClC-3、α 7整联蛋白链和睾丸特异性β-样蛋白BAT 1的小鼠。此外，已经产生了在心脏中过度表达氯离子通道ClC-3的长和短同种型的小鼠。目前，在转基因核心中采用了产生ClC-3和钾离子通道TREK 1的组织特异性（cre/lox）或诱导性（四环素）敲除小鼠的技术。转基因核心由三部分组成。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靶向服务。第二，显微注射设备进行原核和胚泡注射。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。在下一个资助期内，COBRE研究者的转基因核心将产生过表达或缺乏心脏氯离子通道（例如ClC-2、Bestrophin）、心脏整联蛋白链（β 1和α 7整联蛋白）和调节蛋白（活化C激酶受体（RACK 1）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离子通道活性改变对心脏功能的病理生理后果。

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.