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对高致病性新出现的呼吸道病毒易感性中的作用。具体来说，Core将生成经过优化的小鼠系，用于对宿主基因对呼吸道病毒易感性的影响进行无偏倚的全基因组测试。这些系的设计使得小鼠可以被复制来测试时间效应，每个系都同样兼容使用普通免疫试剂，并且整个群体具有最大水平和随机分布的功能相关遗传多态性。小鼠将通过杂交或杂交重组自交系从已知的群体中获得，称为协作杂交。协作交叉是一个哺乳动物参考种群，旨在为最流行的哺乳动物模式生物（小鼠）的系统遗传学提供一个跨学科平台，并克服现有平台的局限性。Core还将定期更新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，每个项目有150个CC系，这些系是控制宿主对呼吸道病毒遗传易感性的基因座的优化全基因组图谱；2)生成基线免疫学参数数据，用于跨项目的病例对照比较；3)生成并维护本项目使用的小鼠系基因组序列的季度更新；4)生成并分发优化的小鼠，用于项目第二阶段的验证研究。

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.