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。具体地说，Core将产生优化的小鼠品系，以无偏见地在全基因组范围内测试宿主遗传学对呼吸道病毒易感性的影响。这些品系的设计使小鼠可以复制以测试时间效应，每一品系都与常用免疫试剂的使用平等兼容，并且总体种群具有最高水平和随机分布的功能相关基因多态。小鼠将通过杂交或异交从被称为合作杂交的群体中获得重组近交系。协作十字是一个哺乳动物参考种群，旨在为最受欢迎的哺乳动物模式生物--小鼠的系统遗传学提供一个跨学科的平台，并克服现有平台的限制。Core还将定期更新本项目中使用的小鼠基因组的详细程度和准确性，从非常密集的基因类型开始，最终对每个品系的整个基因组序列进行重新组装。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优化的全基因组定位的基因座；2)生成用于基线免疫学参数的数据，以用于跨项目的病例对照比较；3)生成和维护本项目使用的小鼠品系的基因组序列的季度更新；4)生成和分发为项目第二阶段的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.