In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01 Clinical Trial Not Allowed) | PAR 23 074

Opportunity Information: Apply for PAR 23 074

This NIH funding opportunity (PAR-23-074) is an R01 grant announcement that supports in-depth phenotyping and related research using knockout mouse strains produced by the International Mouse Phenotyping Consortium (IMPC), including strains generated through the NIH Knockout Mouse Phenotyping Program (KOMP2). The central idea is to help researchers take advantage of these community-generated knockout lines, particularly those that show embryonic lethality, perinatal lethality, or subviability, by encouraging additional, deeper analysis beyond the standardized baseline phenotyping the IMPC routinely conducts. The FOA is explicitly labeled "Clinical Trial Not Allowed," meaning the work is expected to be preclinical and focused on animal models and fundamental biology rather than interventional studies in humans.

The scientific motivation behind the program comes from the IMPC mission to build a comprehensive, genome-wide catalog of mammalian gene function. IMPC aims to create a null mutant for every mouse gene and apply broad, standardized phenotyping so the field can systematically connect gene disruption to observable traits. As context for the scale of the resource, the FOA notes that as of the July 19, 2022 IMPC data release, phenotypic data were already available for 8,260 knockout genes. A consistent theme is that these large, standardized datasets are powerful for discovery, but many strains need follow-up work to pinpoint mechanisms, define developmental timing, and connect early lethality to specific organ system defects or molecular pathways. This FOA is meant to drive that next step.

A special emphasis is placed on knockout strains that do not survive to adulthood or survive poorly, because those lines are often under-explored relative to viable adult knockouts. The FOA highlights that a meaningful subset of IMPC-generated knockouts are expected to be embryonic lethal, perinatal lethal, or subviable. While the text mentions "about 30" strains in this category, the practical message is broader: lethality and reduced viability are common outcomes for complete loss-of-function in essential genes, and those models can be exceptionally informative for understanding developmental biology and disease-relevant pathways. The FOA also points out an important opportunity in genetics: even when homozygous knockout animals are lethal, heterozygous animals are frequently viable and may show measurable phenotypes. That opens the door to studying gene dosage effects, haploinsufficiency, sensitized backgrounds, and subtle organ system changes that may mirror human genetic variation.

In terms of what applicants are being encouraged to do, the announcement is aimed at projects that either (1) extend phenotyping in a more detailed or specialized way, and/or (2) carry out hypothesis-driven research using these IMPC knockout lines to understand the biological basis of the observed phenotypes. The appeal is that these mice are already being created, validated, and bred as part of an international production and phenotyping pipeline, so the community can leverage that investment. Researchers can align their work with strains as they emerge from the IMPC pipeline, enabling timely deep dives into developmental stages, tissue-specific effects, pathogenesis, and mechanistic follow-up that the standardized IMPC pipeline is not designed to cover at scale.

Administrative details in the source information describe the mechanism and basic boundaries. The funding instrument is a grant, and the activity code is R01. The sponsoring agency is the National Institutes of Health. The opportunity is categorized under Health, Income Security and Social Services, with CFDA numbers listed as 93.121, 93.313, and 93.865. The listed award ceiling is $499,999, indicating an upper bound on the amount expected per award under this announcement. The original closing date is January 7, 2026, and the record creation date is January 12, 2023.

Eligibility is broad and includes many types of domestic institutions and organizations: state, county, and local governments; 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; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits both with and without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-U.S. entities (foreign organizations) as well as regional organizations. The inclusion of foreign organizations and regional entities reflects the international, consortium-driven nature of IMPC resources and the broad research community it serves.

Taken together, the opportunity is essentially a call to use a large, standardized, publicly valuable mouse knockout pipeline as a springboard for deeper, more targeted studies of gene function, with a particular focus on lines where complete loss of the gene causes death around birth or earlier, or where animals survive at reduced rates. The program frames these models as uniquely informative and time-sensitive resources: since the IMPC is actively generating and breeding these strains for adult phenotyping, investigators have a window to coordinate additional experiments, capture developmental phenotypes, and produce mechanistic insights that complement and enhance the consortium dataset and ultimately support interpretation of 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 2023-01-12.
• 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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