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Knockout Mouse Phenotyping Program (KOMP2)

The Knockout Mouse Phenotyping Project (KOMP2) is a trans-NIH initiative that aims to generate a comprehensive and public resource comprised of knockout information for all protein-coding genes in the mouse genome.

Overview

Humans share most of their genes with mice.  Because of this, the laboratory mouse has served as a key model organism to help scientists understand much about normal human biology and many diseases. Knocking out the activity of a gene provides valuable clues about what that gene normally does. Researchers can then observe the characteristics of knockout mice to obtain information to help researchers better understand how a similar gene may cause or contribute to disease in humans.

 

Attendees of the “Mouse Genome-wide Targeted Mutagenesis” meeting at the CSHL Banbury Center In 2003

 

The Knockout Mouse Project (KOMP) was initiated in 2006 and aimed to develop knockout mutations for every protein-coding gene in the mouse genome. In a five-year collaboration with the International Knockout Mouse Consortium (IMKC), KOMP centers produced 8,500 of the 17,500 total knockouts in embryonic stem cells.

Launched in 2011 as a Common Fund and Trans-NIH program, the Knockout Mouse Phenotyping Project (KOMP2) is the second phase of the large-scale mouse mutagenesis effort. Now a trans-NIH initiative with support from 18 institutes and centers, KOMP2 aims to generate a comprehensive and public resource comprised of null mutant mice and their phenotype information. As part of the International Mouse Phenotyping Consortium (IMPC), KOMP2 has generated and phenotyped over 5,500 mouse lines using ES cells and CRISPR technology. In the next five years of the project, KOMP2 will work with the IMPC to additionally phenotype at least 1,200 of 3,000 high-priority genes known to exist in both humans and mice.

Program Goals

  1. Design, produce and systematically phenotype a null mutation mouse line across the mouse–human orthologous genome to provide insights into gene function, disease genetics, pleiotropy and co-morbidity.

    • KOMP2 and IMPC have developed standardized pipelines for phenotyping knockout mouse strains at embryo, early adult and late adult stages. Null alleles are produced in numerous ways, with an expanded focus on CRIPSR technology to increase the output of mouse mutants.
  1. Prioritize mouse–human orthologous genes and their proteins that are poorly understood with no or minimal knowledge on biological function and limited tools for their analysis (the “dark genome”).
     
    • Over 16,000 genes in mice have been identified as existing in both humans and mice. KOMP2 and IMPC have produced at least 9,700 of the approximately 13,000 knockout strains that currently exist, leaving 3,000 genes to be prioritized in the mutagenesis effort.  
  1. Partner with the human genetics and clinical community to produce bespoke mouse mutants with human disease-associated coding variants to confirm pathogenicity, susceptibility or resistance to infection and accelerate research and discovery.
     
    • KOMP2 extends its impact through several collaborations with large-scale research projects and programs, including:
       
      1. Gabriella Miller Kids First Pediatric Research Program (NIH Common Fund): KOMP2 and Kids First are collaborating on a pilot project to create mouse strains to study, phenotype and validate coding and non-coding genetic variants (e.g., missense, structural variants, copy number variants, INDELS and frameshifts) identified from Kids First datasets. The IMPC and Kids First will continue to collaborate, investigating more genes to find links between birth defects and childhood cancer.
         
      2. Illuminating the Druggable Genome (NIH Common Fund): KOMP2 is generating knockout mouse strains for the IDG project. The IDG project is studying human genes that can be mapped to mouse orthologues. The IMPC can then generate and phenotype knockout mouse models for these orthologues. The IMPC currently has data for 41% of IDG’s target genes across 25 groups of phenotypes, including ageing, reproductive, immunity, craniofacial, nervous, renal, cardiovascular and others.
         
      3. Undiagnosed Disease Network (NIH Common Fund): The UDN uses KOMP2/IMPC data and mouse models to assist diagnoses. The phenotype data can provide evidence to support the pathogenicity of variants associated with rare and undiagnosed disease cases, and mouse models provide resources for functional studies for pathogenicity and therapeutic approaches.
         
  2. Develop and distribute technology and resources that can enhance understanding of the functional relationship between human genetic variation (coding and non-coding), environment and disease. It will also explore in vivo the mechanisms of genetic variation in health and disease.
     
    • KOMP2 and IMPC research yields valuable insights across biomedical research, made evident through nearly 700 publications, the accessibility of information through multiple open-access resources and the use of knockout data in pre-clinical studies and therapeutic target discovery.

Grantee Information

Principle Investigators Institute Title Grant Number

Braun, Robert E

Murray, Stephen A

White, Jacqueline K
The Jackson Laboratory The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2) OD023222

Dickinson, Mary E

Heaney, Jason D
Baylor College of Medicine The BCM Knockout Mouse Production and Phenotyping Project (BCM KOMP2) HG006348
Lloyd, KC Kent University of California, Davis KOMP2-Phase3 Production and Phenotyping by the DTCC Consortium OD023221

Parkinson, Helen E

Groza, Tudor

Mallon, Ann-Marie

Smedley, Damien

Wells, Sara
European Molecular Biology Laboratory  Mouse Phenotyping Informatics Infrastructure - Data acquisition, integration, analysis and translation of high throughput mammalian phenotyping data HG006370

Funding Opportunities

Active

At this time, there are no current funding opportunity announcements. 


Expired

  • RFA-HG-21-037: Limited Competition: Knockout Mouse Phenotyping Project Data Coordination Center and Database (UM1) 
  • RFA-HG-21-036: Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)
  • RFA-RM-15-017: Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)
  • RFA-RM-15-016: Limited Competition: Knockout Mouse Phenotyping Project Database (UM1)
  • RFA-RM-10-013: Knockout Mouse Production and Cryopreservation (U42)
  • RFA-RM-10-012: Knockout Mouse Phenotyping Project Database (U54)
  • RFA-RM-10-011: Knockout Mouse Phenotyping (U54)
  • Funding Opportunities

    Active

    At this time, there are no current funding opportunity announcements. 


    Expired

    • RFA-HG-21-037: Limited Competition: Knockout Mouse Phenotyping Project Data Coordination Center and Database (UM1) 
    • RFA-HG-21-036: Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)
    • RFA-RM-15-017: Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)
    • RFA-RM-15-016: Limited Competition: Knockout Mouse Phenotyping Project Database (UM1)
    • RFA-RM-10-013: Knockout Mouse Production and Cryopreservation (U42)
    • RFA-RM-10-012: Knockout Mouse Phenotyping Project Database (U54)
    • RFA-RM-10-011: Knockout Mouse Phenotyping (U54)

Resources

For more information about the International Mouse Phenotyping Consortium (IMPC), please visit IMPC Consortium and IMPC Workshops.

To learn more about the Mutant Mouse Resource and Research Centers (MMRRC), please visit the MMRRC website.

Staff

Program Directors

Colin Fletcher, Ph.D.
Colin Fletcher, Ph.D.
  • Program Director, The Knockout Mouse Project (KOMP)
  • Division of Genome Sciences
Oleg Mirochnitchenko
Oleg Mirochnitchenko, Ph.D.
  • Health Science Administrator
  • Division of Comparative Medicine, NIH Office of the Director

Program Analysts

Maya Vanzanten
Maya VanZanten, B.S.
  • Scientific Program Analyst
  • Division of Genome Sciences

Last updated: November 18, 2022