Transgenic/Knock-out Mouse

转基因/基因敲除小鼠核心为PPG实现其目标提供了关键手段 了解TIM基因家族的体内功能。核心拥有这两个方面的专业知识 传统和有条件的转基因和敲除技术，将使新的 小鼠品系用于分析TIM分子在体内的功能。核心将由DRS共同管理 埃斯特尔·贝泰利和阿琳·夏普，他们在产生转基因和基因敲除方面拥有丰富的经验 老鼠。贝泰利博士帮助培育了许多TCR转基因小鼠，包括MOG TCR 转基因小鼠(2D2)，并与Mohamed Oukka博士(PI.核心B)，生成 FOX-P3.GFP基因敲除小鼠。Arlene Sharpe博士是迄今为止在产生基因敲除小鼠方面的世界领导者 产生了20多只基因敲除小鼠，包括缺乏共刺激分子和TIM分子的小鼠。 贝泰利博士和夏普博士将共同培育和提供许多缺乏时间的小鼠品系 分子与不同的项目。 我们的具体目标是： 1)产生过表达Tim基因的转基因菌株，无论是结构性的还是诱导性的； 过表达TIM3的转基因小鼠的产生将是我们最初的关注点。 2)建立新的缺乏TIM家族成员的小鼠品系：TIM-3基因缺陷小鼠和 TIM1/TIM2双缺陷小鼠将是我们最初关注的焦点。 3)创造新的小鼠品系，便于利用育种时间分析TIM基因的功能 转基因或TIM缺陷小鼠与细胞因子报告鼠；TIM 3“‘x IL-17，TIM 3”’“x的产生 IL-10和TIM 3“‘x FoxPS报告菌株将是我们最初关注的焦点。 4)维持并提供现有转基因、“敲除”和同源品系的小鼠给PPG 调查人员 这些研究不仅对TIM家族成员在调节T细胞中的作用提供了深入的了解 体内的激活和耐受，但也可能提供治疗操作的关键信息 这些关键的免疫调节分子。

The Transgenic/Knockout Mouse Core provides a critical means by which the PPG will achieve its goal of understanding the in vivo functions of the TIM gene family. The Core has the expertise with both conventional and conditional transgenic and knockout technology that will enable the generation of novel mouse strains for analyzing the functions of TIM molecules in vivo. The core will be jointly managed by Drs Estelle Bettelli and Arlene Sharpe, who have extensive experience in generating transgenic and knock-out mice. Dr. Bettelli was instrumental in generating many of the TcR transgenic mice including MOG TcR transgenic mouse (2D2) and in addition in collaboration with Dr. Mohamed Oukka (PI. Core B), generated Fox-P3.GFP knock-in mice. Dr. Arlene Sharpe is a world leader in generating knock-out mice has thus far generated over two dozen knock-out mice including mice deficient in costimulatory and TIM molecules. Together, Dr. Bettelli and Dr. Sharpe will generate and provide many of the mouse strains deficient in TIM molecules to various projects. Our specific aims are: 1) To generate transgenic strains that overexpress TIM genes, either constitutively or inducibly; the generation of transgenic mice that over-express TIM 3 will be our initial focus. 2) To generate novel mouse strains lacking TIM family members; the generation of TIM 3 deficient mice and TIM1/TIM 2 double deficient mice will be our initial focus. 3) To generate novel mouse strains that facilitate the analysis of the TIM gene function by breeding TIM transgenic or TIM deficient mice with cytokine reporter mice; the generation of TIM 3"'" x IL-17, TIM 3"'" x IL-10 and TIM 3"'" x FoxPS reporter strains will be our initial focus. 4) To maintain and provide mice of existing transgenic, "knock-out" and congenic strains to PPG investigators These studies will not only provide insights into the roles of TIM family members in regulating T cell activation and tolerance in vivo, but also may provide information critical for therapeutic manipulation of these key immunoregulatory molecules.