Mouse and ENU Core

本计划项目赠款的总体目标(P01)是定义多个 细胞内病原体和受感染的宿主细胞。在过去的10年里，许多宿主先天免疫 已经确定了感知微生物感染的途径。控制细胞生长的受体 这些途径的激活包括Toll样受体(TLRs)和一个不断壮大的胞浆家族 受体包括NODS、NAIPS、NALPS和多个胞质核酸传感器。重要的是， 这些途径中的每一个在微生物感染期间的贡献将根据组成的不同而不同， 生活方式，以及这种微生物的毒力机制。 这个P01的核心B将维持一群先天成分缺乏的小鼠品系 免疫或其他对研究先天免疫有用的基因修饰。内核B还支持 基于enu的正向遗传筛选寻找单核细胞增多性李斯特菌寄主防御相关新基因， 嗜肺性乳杆菌和结核分枝杆菌感染。小鼠和从这些小鼠衍生的巨噬细胞 分发给P01内的每个项目。所有品系的小鼠都已经或将要回交到 C57B1/6等位基因背景。酷睿B将降低鼠标的总体成本，因为 规模经济。此外，每个P01项目都将受益于使用基因较少的细胞和小鼠 和实验性的变种。

The overall goal of this Program Project Grant (P01) is to define the key interactions between multiple intracellular pathogens and infected host cells. Over the last 10 years, many of the host innate immune pathways involved in sensing microbial infection have been identified. The receptors controlling the activation of these pathways include the Toll-like receptors (TLRs) and a growing family of cytosolic receptors including Nods, Naips, Nalps, and multiple cytosolic nucleic acid sensors. Importantly, the contribution of each of these pathways during a microbial infection will differ based on the composition, lifestyle, and virulence mechanisms of that microbe. Core B of this P01 will maintain a colony of mouse strains with deficiencies in components of innate immunity or other genetic modifications useful for the study of innate immunity. Core B also supports an ENU-based forward genetic screen to identify new genes involved in host defense during L. monocytogenes, L. pneumophila, and M. tuberculosis infection. Mice and macrophages derived from these mice will be distributed to each of the projects within the P01. All mouse strains have been or will be backcrossed onto the C57B1/6 genetic background to equivalent degrees. Core B will reduce overall mouse costs due to economies of scale. In addition, each P01 project will benefit from using cells and mice with fewer genetic and experimental variations.