Animal Models Core

动物模型核心的最终目标是支持一个高度互动的项目，该项目将探索和解释自然变异在高致病性、新出现的呼吸道病毒易感性中的作用。具体而言，核心将产生优化的小鼠品系，用于无偏倚的全基因组检测宿主遗传学对呼吸道病毒易感性的影响。这些品系的设计使得小鼠可以被复制以测试时间效应，每个品系与普通免疫试剂的使用同等相容，并且总体群体具有功能相关遗传多态性的最大水平和随机分布。小鼠将通过来自被称为协作杂交的群体的重组近交系进行杂交或异交而衍生。协作交叉是一个哺乳动物参考群体，旨在为最流行的哺乳动物模式生物小鼠的系统遗传学提供跨学科平台，并克服现有平台的局限性。核心还将定期更新本项目中使用的小鼠基因组的细节和准确性，从非常密集的基因型开始，最终从头组装每个品系的全基因组序列。我们的具体目标是：1）生成并分发给四个科学项目中的每一个，其中150个CC系是控制宿主对呼吸道病毒的遗传易感性的基因座的优化的全基因组作图; 3）生成并维护本项目所用小鼠品系基因组序列的季度更新，以及4）在项目的第二阶段，生成并分发为验证研究优化的小鼠。

The ultimate objective of the Animal Models Core is to support a highly interactive program that will explore and explain the role of natural variation in susceptibility to highly pathogenic, newly emerging respiratory viruses. Specifically the Core will generate mouse lines that are optimized for unbiased genome-wide testing of the effect of host genetics in susceptibility to respiratory viruses. These lines are designed such that mice can be replicated to test temporal effects, every line is equally compatible with use of common immunological reagents and the overall population has maximum level and random distribution of functionally relevant genetic polymorphisms. Mice will be derived by intercrossing or out crossing recombinant inbred lines from population known as the Collaborative Cross. The Collaborative Cross is a mammalian reference population that was designed to provide a cross-disciplinary platform for systems genetics in the most popular mammalian model organism, the mouse, and to overcome limitations of existing platforms. The Core will also provide regular updates with increasing levels of detail and accuracy on the genome of the mice used in this project starting with very dense genotypes and ultimately de novo assembly of the whole genome sequence of each line. Our specific aims are: 1) Generate and distribute to each of the four scientific projects with 150 CC lines that are optimized genome wide mapping of loci that control host genetics susceptibility to respiratory viruses; 2) Generate data for baseline immunological parameters to be used case-control comparisons across projects; 3) Generate and maintain quarterly updates of the genome sequence of mouse lines used on this project and 4) Generate and distribute mice that are optimized for validation studies in the second phase of the project.