The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)

项目总结 杰克逊实验室(JAX)基因敲除小鼠表型项目第二阶段(KOMP2)的目标是 为创建获得的哺乳动物基因功能的全面目录的国际努力作出贡献 通过创建基因敲除和执行高通量表型鉴定管道。在JAX AN 早期成人管道(EAP)正被用于对17周龄以下的小鼠进行表型鉴定，目标是筛选1000只 在当前5年项目期结束前培育突变株系。此外，在本颁奖期间，150人的子集 LINES正在老化到18个月，并使用晚期成人管道(LAP)检测与年龄相关的表型 表型。不能存活和亚存活的品系也正在使用特殊的胚胎表型进行表型鉴定 管道。2020年3月11日，世界卫生组织(WHO)宣布爆发严重急性呼吸道综合征 呼吸综合征冠状病毒2型(SARS-CoV-2)病(新冠肺炎)是一种世界性的大流行.一种后果 大流行的主要原因是减少了我们实现最初目标所需的现有人员和服务。 大流行期间的限制限制了JAX KOMP2中心的繁殖和表型活动。 我们保持了较低的队列繁育水平，并减少了小鼠的表型。此外，为了 为了最大限度地扩大物理距离并以一种缓解病毒传播和传播的方式运作，我们有 要求工作人员密切接触的停产程序。由于大流行，我们缺少总的 所有测试中预计已表型的行数和具有完整队列的行数。这个 请求将供资延长至当前项目期之后的目的是完成初步目标 创造了1000个KO小鼠品系并进行了表型鉴定。我们预计，在最初的赠款期限结束时， 860个品系的小鼠将完成EAP管道，所有150个品系的LAP表型数据将 收好了。这一资金支持的扩展的具体目标是从剩余的140人中培育和填充EAP 鼠标线，使我们的总数达到1000线。大约70%的线路(~100条线路)将完全可行 因此将被鉴定为纯合子。其余30%的线路(~40条线路)是不可行的或 不可行，因此将以杂合子的形式进入EAP。这40行还将用于填充我们的 胚胎致死表型流水线。将对EAP和LAP数据执行QC分析并将其导出 至国际老鼠表型鉴定联盟数据协调中心。

PROJECT SUMMARY The goal of The Jackson Laboratory (JAX) Knockout Mouse Phenotyping Project phase 2 (KOMP2) is to contribute to the international effort of creating a comprehensive catalog of mammalian gene function obtained through the creation of gene knockouts and execution of a high-throughput phenotyping pipeline. At JAX an Early Adult Pipeline (EAP) is being used to phenotype mice up to 17 weeks of age with a goal of screening 1,000 mutant lines by the end of the current 5-year project period. Further, during this award period, a subset of 150 lines is being aged out to 18 months and phenotyped using a Late Adult Pipeline (LAP) to detect age-associated phenotypes. Nonviable and subviable lines are also being phenotyped using specialty embryonic phenotyping pipelines. On March 11, 2020 the World Health Organization (WHO) declared the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) a world-wide pandemic. A consequence of the pandemic has been a reduction of our available personnel and services needed to reach our original goals. Restrictions during the pandemic have curtailed the breeding and phenotyping activity on the JAX KOMP2 center. We have maintained a lower level of breeding of cohorts and reduced phenotyping of mice. In addition, in order to maximize physical distancing and operate in a way that mitigates viral transmission and spread, we have discontinued procedures that require close contact between staff. Due to the pandemic, we are short of the total number of lines projected to have been phenotyped and on the number of lines with full cohorts for all tests. The purpose of this request for a funded extension beyond the current project period is to complete the initial goals of creating and phenotyping 1000 lines of KO mice. We project that at the end of the original grant period that 860 lines of mice will have completed the EAP pipeline and that LAP phenotyping data from all 150 lines will be collected. The Specific Aims of this funded extension are to breed and populate the EAP from the remaining 140 mouse lines to bring our total to 1000 lines. Approximately 70% of the lines (~100 lines) will be fully viable and will therefore be phenotyped as homozygotes. The remaining 30% of the lines (~40 lines) be non-viable or subviable and will therefore enter the EAP as heterozygotes. These 40 lines will also be used to populate our embryo lethal phenotyping pipeline. QC analysis will be performed on both the EAP and LAP data and exported to the Data Coordination Center of the International Mouse Phenotyping Consortium.