In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01 Clinical Trial Not Allowed) | PAR 20 137

Opportunity Information: Apply for PAR 20 137

This grant opportunity, PAR-20-137, is an NIH R01 funding announcement focused on getting more scientific value out of knockout mouse strains being produced by the International Mouse Phenotyping Consortium (IMPC), including the NIH Knockout Mouse Phenotyping Program (KOMP2). The core idea is to support researchers who want to do deeper phenotyping and hypothesis-driven studies on IMPC-generated knockout (KO) lines that are embryonic lethal, perinatal lethal, or subviable. These are strains where homozygous knockout animals often cannot survive to adulthood, which means standard adult phenotyping pipelines may not capture what the gene is doing. By funding additional, targeted work while these lines are actively being created and bred, NIH aims to accelerate functional understanding of essential genes and the biological pathways that underlie early development and survival.

The scientific motivation ties directly to the IMPC mission: building a comprehensive catalog of mammalian gene function that can serve as a reference for interpreting human genetic variation. The FOA highlights the scale and momentum of the IMPC effort, noting that by November 2019 the IMPC-KOMP2 pipeline had already generated mutants in 9,051 mouse genes, completed phenotyping for 7,153 lines, and released data for 6,255 lines corresponding to 5,861 mutant genes. The longer-term goal is broad phenotyping for roughly 20,000 knockout strains. Within that large set, a meaningful fraction of lines are expected to show embryonic or perinatal lethality or reduced viability, and those outcomes often signal that the knocked-out gene plays an essential role in development or early-life physiology. The FOA also points out a practical and scientific opportunity: even when homozygous mutants are lethal, heterozygous animals frequently survive and can show informative phenotypes, making them valuable for understanding dosage sensitivity, partial loss-of-function effects, and disease-relevant biology.

In terms of what NIH is trying to fund, the announcement encourages applications that either (1) conduct in-depth phenotyping beyond what the IMPC baseline pipeline provides, and/or (2) pursue mechanistic or functional research that uses these lethal/subviable knockout lines to answer specific biological questions. In plain terms, applicants are expected to leverage IMPC resources and the existence of these strains to produce richer developmental, anatomical, physiological, molecular, or systems-level characterization than would otherwise be available. Because these lines are generated through a coordinated consortium, the FOA is essentially inviting the broader research community to “plug in” specialized expertise, tools, and assays to extract insights that standard high-throughput screening cannot fully cover, especially when the phenotype involves embryogenesis, perinatal transition, or survival-related traits.

Administrative details in the source information frame how the opportunity is structured. It is a discretionary grant mechanism using the R01 activity code, and it is explicitly labeled “Clinical Trial Not Allowed,” meaning the supported work is intended to be preclinical and focused on animal models and related experimental biology rather than human interventional studies. The sponsoring agency is the National Institutes of Health. The opportunity is listed under CFDA numbers 93.121, 93.313, and 93.865, reflecting the NIH’s cataloging of related funding areas. The FOA creation date is March 12, 2020, and the original closing date shown is November 5, 2022. The provided award ceiling is $499,999. An expected number of awards is not specified in the supplied text, which typically means applicants should not assume a particular funding volume and should instead focus on proposing a strong, well-justified project aligned with the FOA goals.

Eligibility is broad and intentionally inclusive, spanning many types of institutions and organizations. Eligible applicants include various levels of government (state, county, city/township, special districts), independent school districts, public and state-controlled higher education institutions, private higher education institutions, federally recognized 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 calls out additional eligible applicant types 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), eligible federal agencies, faith-based or community-based organizations, non-U.S. (foreign) organizations, regional organizations, and U.S. territories or possessions. Overall, the eligibility language signals an intent to encourage participation from a wide research ecosystem, including institutions that may bring specialized expertise in developmental biology, genetics, pathology, imaging, computational phenotyping, or disease modeling.

In summary, PAR-20-137 is designed to expand the scientific return on investment from the IMPC/KOMP2 knockout mouse production pipeline by funding researchers to take embryonic/perinatal lethal or subviable knockout strains further than standard screening can. The announcement emphasizes the importance of understanding essential genes, leveraging both lethal homozygotes (where possible to study during embryonic stages) and viable heterozygotes, and producing deeper functional data that will help the community interpret gene function and human genetic variants.

• 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 2020-03-12.
• Applicants must submit their applications by 2022-11-05. (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.

Apply for PAR 20 137

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