Mouse Models Containing Human Alleles Novel Tools to Study Brain Function (R21/R33) | Apply Online

Opportunity Summary:

The grant opportunity titled "Mouse Models Containing Human Alleles: Novel Tools to Study Brain Function (R21/R33)" (Funding Opportunity Number PAR-08-158) is an NIH funding announcement designed to push forward the creation of new mouse models that carry human genes or human genetic elements. The central idea is to support research tools that more closely mirror human biology in order to clarify how specific genes and gene regulatory components shape brain function. These models are meant to help researchers move beyond broad associations and instead test how particular human gene variants, as well as gene dosage changes (such as deletions, duplications, or altered copy number), actually affect physiology and behavior in ways that may contribute to mental disorders, substance use disorders and addiction, neurodegenerative conditions associated with aging, and alcohol use disorder, including related comorbid conditions.

This program is sponsored by multiple NIH Institutes that share an interest in brain- and behavior-related disease mechanisms: the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA). That combination signals that the mouse models proposed under this FOA should be broadly useful across psychiatric, addiction, and aging-related neurobiology, and that they should be built and characterized in a way that makes them informative for mechanistic studies rather than being purely descriptive.

Funding is provided through the NIH Exploratory/Developmental Phased Innovation mechanism (R21/R33). This is a two-stage structure where applicants submit one application that includes both phases, but the work is intentionally staged. The first stage (R21) supports early development and feasibility work, such as generating the model, demonstrating that the human allele or human genetic element is correctly introduced and expressed, and establishing initial validation data. The second stage (R33) is intended for the next step of the project once the R21 milestones are met, supporting expanded characterization and deeper analysis of the model, such as more comprehensive molecular, cellular, physiological, and potentially behavioral profiling relevant to brain function and disease mechanisms. Practically, the phased structure is meant to reduce risk for both the applicant and NIH by funding ambitious model development while still requiring clear progress before moving into the more advanced phase.

The FOA emphasizes both development and characterization, which matters because NIH is not only paying for a new strain to be created, but also for evidence that the model works as intended and is informative. In this context, "humanized" mouse models can include mice engineered to carry human coding variants, human regulatory DNA elements that control when and where genes are expressed, or other human genetic components that may influence gene function in the brain. The specific motivation is that many risk signals in human studies involve subtle sequence variation or dosage changes, and mouse models that incorporate those human elements can provide a controlled way to test causal effects and map biological pathways.

The award details in the source information describe it as a discretionary grant program in the health category (CFDA 93.242, Mental Health Research Grants) with no cost-sharing or matching requirement. The listed award ceiling is $150,000, and awards depend on the availability of funds and the quality and volume of applications received, which is standard language indicating there is no guaranteed number of awards. The announcement was posted April 24, 2008, created December 5, 2008, and had an original and current closing date of January 28, 2011, with an archive date of February 28, 2011, meaning it is a historical funding opportunity rather than an active one today.

Eligibility is broad and includes many types of institutions and organizations. Eligible applicants include public and private institutions of higher education, nonprofit organizations (including those with and without 501(c)(3) status), for-profit organizations (other than small businesses as well as small businesses), and a range of government entities such as state, county, city/township, special district governments, and independent school districts. The eligibility list also explicitly includes tribal organizations (federally recognized and other than federally recognized), tribally controlled colleges and universities, U.S. territories or possessions, public housing authorities/Indian housing authorities, and regional organizations. Importantly, the FOA also allows non-U.S. entities (foreign organizations) and federal agencies as eligible applicants, and it calls out categories such as HBCUs, Hispanic-serving institutions, and Alaska Native and Native Hawaiian-serving institutions, reinforcing that a wide range of research organizations could apply.

For applicants looking for the complete announcement and requirements, NIH provided an additional information link to the full FOA text at http://grants.nih.gov/grants/guide/pa-files/PAR-08-158.html. The contact information provided is oriented toward technical access and linking issues, directing users to the NIH Office of Extramural Research (OER) webmaster support email.

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