In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01) | PAR 17 005

Opportunity Information: Apply for PAR 17 005

The NIH grant opportunity "In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01)" (Funding Opportunity Number PAR-17-005) is designed to push the field beyond standard, broad screening by supporting deeper biological investigation of a specific, high-value subset of knockout mouse lines. These are knockout (KO) strains being produced through the International Mouse Phenotyping Consortium (IMPC), a global effort to generate and characterize large numbers of gene knockouts in a systematic way. The NIH Knockout Mouse Phenotyping Program (KOMP2) is part of the IMPC, and the FOA emphasizes taking advantage of the moment when these lines are already being created, bred, and run through baseline adult phenotyping pipelines, making it more efficient for the research community to add targeted in-depth studies.

The scientific focus is on KO strains that show embryonic lethality, perinatal lethality, or subviability. In practical terms, these are lines where homozygous knockout animals die before birth, around birth, or survive at reduced rates, which often prevents them from being fully assessed in standard adult phenotyping screens. Even so, these lines can be exceptionally informative because they frequently point to genes that are essential for development, organogenesis, and early-life physiological systems. The FOA also highlights an important genetic reality: while homozygous mutants may be lethal, many of these mutations are expected to produce measurable and informative phenotypes in viable heterozygous animals. That creates a clear opportunity to study gene dosage effects and partial loss-of-function biology that can be directly relevant to human disease, where heterozygous variants are common.

This announcement encourages applicants to carry out phenotyping and/or hypothesis-driven research using these IMPC-generated strains, with an emphasis on more detailed follow-up than the standardized IMPC pipelines typically provide. The central idea is to leverage the existing infrastructure and ongoing breeding/production efforts within IMPC and KOMP2, and then layer on additional experiments that clarify developmental timing of lethality, affected tissues and organ systems, cellular and molecular mechanisms, and any detectable phenotypes in heterozygotes or conditional contexts. The program description frames this as a unique window of opportunity because the lines are already in motion through a large international pipeline, reducing duplicative effort and accelerating discovery if outside investigators step in to perform deeper characterization.

The broader context included in the FOA underscores the scale and pace of IMPC and KOMP2 production. KOMP2 had generated roughly 2,500 mouse strains at the time described, with plans to create about 6,000 more over the following five years, contributing to the IMPC goal of broad-based phenotyping for around 20,000 KO strains overall. Within that massive set, the FOA notes that a subset (described as about 30 strains in the provided text) are or are expected to be embryonic or perinatal lethal or subviable, and it is this subset that motivates the call for targeted, in-depth work because routine adult phenotyping alone cannot capture the key biology for these lines.

From an administrative standpoint, the opportunity is an NIH discretionary grant using the R01 mechanism, categorized under Health, Income Security and Social Services, and associated with CFDA numbers 93.121 and 93.865. The source data lists an award ceiling of $499,999. The opportunity was created on 2016-10-07, and the original closing date provided is 2019-11-05. While the summary here focuses on the purpose and scope, these details matter for understanding how the announcement was structured and the general magnitude of support anticipated per award.

Eligibility is broad and intentionally inclusive, spanning many types of U.S.-based institutions and organizations as well as certain non-U.S. entities. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other categories. The FOA also explicitly names additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; non-domestic (non-U.S.) entities (foreign organizations); regional organizations; Indian/Native American Tribal Governments other than federally recognized; and U.S. territories or possessions. This wide eligibility aligns with the program goal of maximizing scientific uptake of these valuable mouse resources across the research community.

Overall, this FOA is essentially a call to take rare, information-rich knockout mouse lines that cannot be fully understood through standard adult screens because of early lethality or reduced viability, and to fund investigators who can perform the deeper phenotyping and mechanistic studies needed to translate those genotypes into clear biological insight. By tying the work directly to IMPC/KOMP2-generated strains, the program aims to speed discovery, reduce redundancy in model generation, and extract as much developmental and disease-relevant knowledge as possible from knockout lines that are otherwise difficult to study.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.865.
• This funding opportunity was created on 2016-10-07.
• Applicants must submit their applications by 2019-11-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $499,999.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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