Mouse and ENU Core

本计划项目补助金（P01）的总体目标是定义多个项目之间的关键互动， 细胞内病原体和感染的宿主细胞。在过去的10年里，许多宿主的先天免疫 已经鉴定了涉及检测微生物感染的途径。受体控制着 这些途径的激活包括Toll样受体（TLR）和越来越多的细胞溶质受体家族。 受体，包括Nods、Naips、Nalps和多个胞质核酸传感器。重要的是 这些途径中的每一种在微生物感染期间的贡献将基于组成而不同， 生活方式和致病机制。 该P01的核心B将维持具有先天免疫缺陷的组分缺陷的小鼠品系的集落。 免疫或其他遗传修饰，用于先天免疫的研究。核心B还支持 基于ENU的正向遗传筛选，以确定新的基因参与宿主防御在L。单核细胞增多症， L. pneumophila和M.肺结核感染。小鼠和来自这些小鼠的巨噬细胞将被 分配给P01中的每个项目。所有小鼠品系都已经或将要回交到 C57 B1/6遗传背景的程度相当。核心B将降低总体鼠标成本，因为 规模经济此外，每个P01项目都将受益于使用具有更少遗传缺陷的细胞和小鼠。 和实验变异。

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.