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

The NIH has issued a Notice of Funding Opportunity (NOFO) titled "In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability" (PAR-25-140). This grant opportunity, under the R01 Research Project Grant mechanism, is designed to support phenotyping and research on embryonic lethal, perinatal lethal, or subviable knockout (KO) mouse strains created by the International Mouse Phenotyping Consortium (IMPC), of which NIH’s Knockout Mouse Phenotyping Program (KOMP2) is a part. The purpose of this NOFO is to expand the research potential of IMPC-generated KO mouse models, leveraging their unique relevance to understanding congenital human diseases, infertility, spontaneous miscarriage, and structural birth defects. The NOFO invites applications that fall within three primary categories: (1) non-hypothesis-driven phenotyping or screening of IMPC-generated strains, such as detailed imaging and expression profiling, (2) combination of non-hypothesis-driven screening with hypothesis-driven research, or (3) purely hypothesis-driven studies that focus on specific mechanisms underlying lethality or subviability. The NOFO encourages studies that use the IMPC resources to investigate defects in embryonic development, organogenesis, or fertility. Researchers are expected to use the data available from the IMPC for mid-gestational stage KO strains, with additional resources available for later phenotyping stages. Studies under this NOFO may apply various advanced imaging, molecular, and genetic techniques to further characterize these KO models and investigate the underlying gene functions. Budgets for this grant are limited to $499,999 in direct costs per year, with a maximum project duration of five years. This NOFO is open to public and private higher education institutions, non-profit organizations, for-profit organizations, local and state governments, and other entities, including some foreign institutions and components. All applicants must complete registrations in systems such as SAM, eRA Commons, and Grants.gov. The participating NIH institutes—NICHD, NIDCR, and ORWH—each have specific areas of research interest within this NOFO. NICHD is interested in KO strains with relevance to post-implantation development, organogenesis, and placental development. NIDCR seeks studies relevant to craniofacial development, mineralized tissues, and salivary gland function. ORWH emphasizes research that incorporates sex as a biological variable, aligning with NIH's strategic goals for the health of women, especially where sex-specific data and gender influences on health outcomes are relevant. Review criteria include the significance and innovation of the research, rigor and feasibility of the approach, and investigator expertise and resources. Reviewers will assess the potential impact of the research on the field and whether the project effectively leverages the KOMP2/IMPC resources. Applications that plan to generate data for deposition into public repositories are encouraged to include letters of support for this purpose and budget for associated costs. Applications are due by 5:00 PM local time of the applicant’s organization, and prospective applicants are encouraged to submit early to allow time for corrections. This NOFO does not require a letter of intent, but submission of a letter is recommended to assist NIH in planning the review. The first due date for new applications is June 5, 2025, with subsequent annual due dates through January 8, 2026.