Notice of Special Interest (NOSI): Development of Animal Models of Down Syndrome and Related Biological Materials as Part of the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project

Notice Number: NOT-OD-20-017

Key Dates
Release Date: December 18, 2019
First Available Due Date: January 27, 2020
Expiration Date: September 09, 2022

Related Announcements



RFA-OD-19-027, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24 Clinical Trials Not-Allowed)


PAR-19-369, Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed)

NOT-OD-20-012, Notice of Intent to Publish Funding Opportunity Announcements in Fiscal Year 2020 for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project

NOT-OD-20-129 - Notice of Special Interest (NOSI) regarding the Availability of Urgent Competitive Revisions and Administrative Supplements for Research on Coronavirus Disease 2019 (COVID-19) in Individuals with Down Syndrome for the INCLUDE Project

RFA-OD-21-007 - INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Exploratory/Developmental Research Grant Award (R21 Clinical Trial Not Allowed)

Issued by
National Institutes of Health (NIH)
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)



The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018 and 2019 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population while increasing the pipeline of Down syndrome investigators. Information about projects that were funded in 2018 and 2019, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with DS face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though DS is the most common genetic cause of intellectual and developmental disabilities (IDD) and, in the past 25 years, the average lifespan has doubled from 30 to 60 years. In addition to intellectual disability, DS is associated with an increased prevalence of autism and epilepsy. About 75% of individuals with DS experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with DS also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with DS infrequently develop solid tumors such as breast or prostate cancer. Despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, people with DS rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with DS and for individuals who do not have DS but who share these co-occurring conditions.

Research Objectives

The purpose of this Notice of Special Interest (NOSI) is to foster development of and improve the access to animal models of Down syndrome and related materials and information that will advance preclinical and basic science studies related to Down syndrome. Sharing of resources and effective communication of outputs to broader communities are a high priority of the INCLUDE Project. Applicants responding to this NOSI are strongly encouraged to describe plans for rapid sharing of data and results as well as innovative data analytics approaches (see Goal 3, NIH Strategic Plan For Data Science).

Examples of animal models or related materials that may be developed include, but are not limited to:

  • Animal models for studying fundamental biological mechanisms underlying Down syndrome;
  • Genetic resources, antibodies or other reagents for quantifying or characterizing macromolecules or cells in animal models of Down syndrome, systems biology approaches, or informatics tools and resources, including artificial intelligence, machine learning or deep phenotyping tools, for generating novel hypotheses or improving the value of animal models in Down syndrome research;
  • Complementary approaches to the use of animals, such as animal-tissue-on-chip models, that can simulate physiological and pathophysiological processes and capture the complex dynamics of interacting molecules, cells, tissues and organs outside of the whole organism for Down syndrome research.
  • Comparison of existing Down syndrome animal models to best understand the health conditions of individuals with Down Syndrome. While multiple useful animal models are available to the community, a careful comparison of their distinct phenotypes is critical. For example, with the mouse strains presently in use, the penetrance of particular phenotypes would benefit from qualitative and quantitative validation. Other important comparisons could include the effect of background strain and colony maintenance on the genotype and phenotype over time.
  • Development of rat, non-rodent vertebrate, and nonhuman primate models of Down syndrome that are better suited to answer specific questions concerning the complex neurological, behavioral, and other phenotypes that occur in humans with Down Syndrome than currently available mouse models.

The INCLUDE project is particularly interested in development of animal models with relevance to the multiple organ systems affected in individuals with Down syndrome co-occurring conditions, such as neurodevelopment, immune system dysregulation, Alzheimer’s disease, cancer, cardiovascular disease, and autism. Applications for supporting R21 exploratory research projects or R24 resource-related research projects should be directly submitted in response to this NOSI.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. Long-term projects, or projects designed to increase knowledge in a well-established area, are not appropriate for R21 awards. The R21 grant activity is intended to encourage exploratory research projects that foster a constant infusion of new ideas, techniques, and points of view into Down syndrome-related research. Such projects could assess a new experimental system or propose an innovative use of an existing methodology, system or model to enhance Down syndrome-related research. These studies may involve considerable risk but may lead to a breakthrough in Down syndrome research through development of novel techniques, reagents, methodologies and models.

Applications for R24 awards should propose the development of animal models and related resources that would serve broad areas of Down syndrome-related research. The R24 grant activity is intended to encourage resource-related research projects that support basic and preclinical research by providing a substantial amount of readily available animal-related resources. Animal-related resources can include mutant and transgenic animals; related biological materials, such as nucleic acids, proteins, cell lines, and tissues; and knowledge of an animal’s genome, life cycle, molecular, cellular and physiological phenotypes, and behaviors.

Program Directors/Principal Investigators (PD/PIs) planning to submit applications in response to this NOSI are strongly encouraged to contact the scientific contacts of this NOSI prior to submission to be advised on appropriateness of the intended resource and research plans for this program, competitiveness of a potential application, and alignment with program priorities of the INCLUDE initiative.

Application and Submission Information

This Notice applies to due dates on or after January 27, 2020 and expires on September 9, 2022.

The following funding opportunity announcements (FOAs) or their reissued equivalents must be used for submissions for this initiative.

Activity Code

FOA Number and Title

First Available Due Date


RFA-OD-19-027, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24 Clinical Trials Not-Allowed)

January 27, 2020


PAR-19-369, Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed)

February 16, 2020

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

For funding consideration, applicants must include NOT-OD-20-017 in the Agency Routing Identifier field (Box 4.b) of the SF 424 (R&R) Form. Applications without this information in Box 4.b will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.


Please direct all inquiries to:

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Charlene Schramm, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: (301) 401-3793

Sige Zou, PhD
Office of Research Infrastructure Programs (ORIP)
Telephone: (301) 435-0749