Oleg Mirochnitchenko
$2,391,665
Stephen A Murray
Jacqueline K White
Jackson Laboratory
Maine
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Eye Institute (NEI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH Office of the Director
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.