In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01 Clinical Trial Not Allowed) | PAR 25 140

Opportunity Information: Apply for PAR 25 140

The National Institutes of Health (NIH) is offering an R01 grant opportunity (PAR-25-140) to support in-depth phenotyping and related research on knockout (KO) mouse strains produced through the International Mouse Phenotyping Consortium (IMPC), including strains generated via the NIH Knockout Mouse Phenotyping Program (KOMP2). The central idea is to help researchers take advantage of IMPC-produced knockout lines that do not survive normally when both copies of a gene are knocked out, meaning the animals are embryonic lethal, perinatal lethal, or subviable. Because these lines can be difficult to study using the standard IMPC adult phenotyping pipeline, the FOA is aimed at funding investigators who can perform deeper, more specialized analyses to extract biological and disease-relevant insight from these challenging models.

This opportunity is grounded in the broader IMPC mission: building a comprehensive, gene-by-gene functional encyclopedia for the mammalian genome, creating null mutants and collecting systematic phenotype data to support interpretation of human genetic variation. As of the IMPC data release cited in the announcement (July 19, 2022), phenotypic data were already available for 8,260 knockout genes, and the consortium is working toward the long-term goal of generating and broadly phenotyping a knockout for every mouse gene. A significant fraction of knockouts are expected to show severe viability issues, with the FOA noting that roughly 30 percent of strains may fall into embryonic or perinatal lethality or subviability categories. Importantly, even when homozygous knockout animals cannot survive, many of these mutations may still produce informative and clinically relevant phenotypes in heterozygous animals, creating a major opportunity for discovery if researchers look beyond the standard adult-homozygous pipeline.

Projects proposed under this FOA are expected to leverage the fact that these strains are actively being created and bred within the IMPC effort. That timing matters: investigators can plug into an existing production and baseline characterization ecosystem, then layer on additional methods to pinpoint when lethality occurs, what developmental systems fail, and what mechanistic pathways are disrupted. In practical terms, responsive applications would typically focus on carefully staged developmental analyses, tissue- and organ-level characterization, specialized imaging or pathology, molecular and cellular profiling, or other targeted experiments that go beyond broad screening to explain why a gene knockout leads to death or reduced survival. The announcement also highlights the scientific value of studying viable heterozygotes for phenotypes that may mirror dosage sensitivity in humans, including subtle developmental, physiological, or disease-relevant changes.

The award mechanism is an NIH R01, and clinical trials are not allowed under this specific announcement, meaning the funded work should be preclinical and focused on mouse model phenotyping and related mechanistic research rather than human intervention studies. The funding instrument type is a grant, and the activity category is within Health, Income Security, and Social Services. The FOA lists an award ceiling of $499,999. The opportunity is categorized as discretionary funding, and it is associated with CFDA numbers 93.121, 93.313, and 93.865.

Eligibility is broad and includes many types of U.S.-based 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; nonprofit organizations with or without 501(c)(3) status (excluding institutions of higher education where applicable); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly calls out additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities/foreign organizations.

Key administrative details provided include the sponsoring agency (NIH), the funding opportunity number (PAR-25-140), and an original closing date of January 7, 2026. The opportunity was created on November 6, 2024. Overall, the FOA is designed to speed up and deepen the functional interpretation of lethal and subviable gene knockouts by enabling the research community to perform focused, high-resolution phenotyping and follow-up biology on IMPC-generated mouse lines that otherwise would be underexplored, despite their strong potential to illuminate essential gene function and mechanisms relevant to human genetic disease.

• 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 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.313, 93.865.
• This funding opportunity was created on 2024-11-06.
• Applicants must submit their applications by 2026-01-07. (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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