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

杰克逊实验室基因敲除小鼠生产和表型项目 (JAX KOMP2)

• 批准号: 10386984
• 负责人: ROBERT E BRAUN
• 金额: $ 239.17万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-11 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386984
• 关键词: 2019-nCoV; Adult; Age; Award; Biological; Breeding; COVID-19; COVID-19 outbreak; Catalogs; Communities; Data; Data Coordinating Center; Disease; Embryo; Encyclopedias; Funding; Genes; Genetic; Goals; Grant; Health; Heterozygote; Homozygote; Human; Human Resources; International; Knock-out; Knockout Mice; Knowledge; Laboratories; Link; Mus; Phase; Phenotype; Procedures; Production; Public Health; Resources; Role; Services; Testing; The Jackson Laboratory; World Health Organization; aged; cohort; data pipeline; gene function; international center; knockout gene; medical specialties; mutant; pandemic disease; phenotypic data; programs; screening; viral transmission

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.

项目摘要 杰克逊实验室（JAX）敲除鼠标表型项目2阶段（KOMP2）的目标是 有助于创建获得哺乳动物基因功能的全面目录的国际努力 通过创建基因敲除和高通量表型管道的执行。在Jax an 早期的成人管道（EAP）用于表型小鼠长达17周龄的小鼠，目的是筛查1,000 当前5年项目期结束时，突变线。此外，在此颁奖期间，150个子集 线条已陈化到18个月，并使用晚期管道（LAP）进行表型，以检测与年龄相关的 表型。使用特种胚胎表型也表现出不可行且可下的线 管道。 2020年3月11日，世界卫生组织（WHO）宣布爆发严重的急性 呼吸道综合征冠状病毒2（SARS-COV-2）疾病（COVID-19）全球大流行。结果 大流行是减少了我们实现我们最初目标所需的可用人员和服务。 大流行期间的限制减少了JAX KOMP2中心的繁殖和表型活性。 我们维持了较低的同类菌种繁殖水平和小鼠表型的降低。另外，按顺序 为了以减轻病毒传播和传播的方式最大化身体距离和操作，我们有 停产的程序需要工作人员之间的密切联系。由于大流行，我们缺乏总数 预计将进行表型的线数，并在所有测试中具有完整队列的线数。这 本请求的目的超出了当前项目期限以外的资助扩展名 创建和表型1000行KO小鼠。我们预测，在原始赠款期结束时 860行小鼠将完成EAP管道，并且所有150行的LAP表型数据将是 集。这项资助的扩展的具体目的是繁殖和填充其余140的EAP 鼠标线使我们的总数达到1000行。大约70％的线（〜100行）将完全可行，并且 因此，将被表型为纯合子。其余30％的线（〜40行）是不可行的或 可亚科，因此将作为杂合子进入EAP。这40行也将用于填充我们的 胚胎致命的表型管道。 QC分析将对EAP和LAP数据进行，并导出 到国际小鼠表型联盟的数据协调中心。