This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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