Transgenic/Knock-out Mouse

转基因/敲除小鼠核心提供了PPG实现其目标的关键手段 了解TIM基因家族的体内功能。核心在这两方面都有专长 常规的和条件性的转基因和敲除技术，这将使得能够产生新的 小鼠品系，用于分析TIM分子在体内的功能。核心将由董事共同管理 Estelle Bettelli和Arlene Sharpe在产生转基因和基因敲除方面具有丰富的经验， 小鼠Bettelli博士在产生包括MOG TcR在内的许多TcR转基因小鼠方面发挥了重要作用 转基因小鼠（2D 2），此外，与穆罕默德Oukka博士（PI.核心B），生成 Fox-P3.GFP敲入小鼠。Arlene Sharpe博士是世界上制造基因敲除小鼠的领导者， 产生了二十多只基因敲除小鼠，包括缺乏共刺激和TIM分子的小鼠。 Bettelli博士和Sharpe博士将共同培育并提供许多缺乏TIM的小鼠品系 分子到各种项目。 我们的具体目标是： 1)为了产生组成型或诱导型过表达TIM基因的转基因菌株; 过度表达TIM 3的转基因小鼠的产生将是我们最初的重点。 2)为了产生缺乏TIM家族成员的新型小鼠品系; TIM 3缺陷型小鼠的产生和 TIM 1/TIM 2双缺陷小鼠将是我们的初步重点。 3)通过培育TIM，产生便于TIM基因功能分析的新型小鼠品系 转基因或TIM缺陷型小鼠与细胞因子报告小鼠; TIM 3“”x IL-17、TIM 3“”x IL-17的产生 IL-10和TIM 3-xFoxPS报告菌株将是我们的初始焦点。 4)维持并向PPG提供现有转基因、“敲除”和同源品系的小鼠 调查人员 这些研究不仅将提供对TIM家族成员在调节T细胞增殖中的作用的见解， 激活和耐受性，而且还可以提供治疗操纵的关键信息。 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.