Equipment to Support Transgenic and Stem Cell Gene Transfer in Mice

转基因小鼠的使用有助于表征和理解哺乳动物发育和生理的遗传基础。耶鲁大学的遗传学小组特别利用转基因小鼠研究了对正常发育至关重要的Hox基因的进化，转录因子AP-2在脊椎动物形态发生中的作用，以及T细胞在免疫系统功能和发育中的作用等项目。这项提案要求提供资金，以扩大耶鲁大学的转基因小鼠设施。该设施目前有一套旧的转基因注射装置和一套用于胚胎干细胞注射的现代装置。转基因装置现在已有20年的历史，尽管机械磨损，但仍在满负荷使用。该项目建议增加一个新的转基因注射站，对现有的仪器进行维修和升级，并增加辅助设备，总体上支持转基因研究和教育的整体计划。随着转基因技术的不断扩大，耶鲁大学的教职员工和学生对该设施的使用也越来越多。大量的实验研究需要购买新的仪器。新的仪器将提高研究和教学活动的效率。额外的设备还将使新技术的开发成为可能，例如转基因的受控表达、产生荧光的报告结构以及通过“敲入”程序修改内源基因。耶鲁大学内外的广泛调查人员和学生都可以获得所需的设备。如果通过将设备存放在由教师研究人员组成的联盟管理的动物研究设施中而不是在单一研究人员小组内来方便访问的话。该设施自给自足，集动物护理、住房和转基因实验室空间于一体。

The use of transgenic mice has been instrumental in the characterization and understanding of the genetic basis of mammalian development and physiology. The genetics group at Yale University in particular has utilized transgenic mice to study the evolution of the HOX genes that are essential for normal development, the role of the transcription factor AP-2 in vertebrate morphogenesis, and the role of T-cells in immune system function and development, among other projects. This proposal requests funds to augment the transgenic mouse facility at Yale University. The facility presently has one old transgene injection set-up and one modern set-up for blastocyst injection of stem cells. The transgene apparatus is now 20 years old and despite mechanical wear and tear is used at capacity. This project proposes to add a new transgene injection station, to repair and upgrade the existing apparatus, and to add ancillary equipment that will generally support the overall program in transgene research and education. As transgene techniques continue to expand, the facility comes under even greater use by the faculty and students at Yale. The sheer volume of experimental studies necessitates the acquisition of new instrumentation. New instruments will enhance the efficiency of both research and teaching activities. Additional equipment will also make possible the development of new techniques such as the controlled expression of transgenes, fluorigenic reporter constructs, and the modification of endogenous genes by "knock-in" procedures. The requested equipment will be accessible to a broad spectrum of investigators and students both within and outside of Yale University. Access if facilitated by housing the equipment in an Animal Research Facility managed by a consortium of faculty investigators rather than within a single investigator's group. The facility is self- contained and integrates both animal care and housing and transgene laboratory space.