Programs and Activities Highlights
- Notice of Funding Opportunity: Informatics, Coordination and Service Center for the Mutant Mouse Resource and Research Centers (U42 Clinical Trial Not Allowed)
The purpose of this notice of funding opportunity is to provide continuing support for the Informatics, Coordination and Service Center (ICSC) unit of the Mutant Mouse Resource and Research Centers (MMRRC) consortium. The ICSC is expected to provide informatics and coordinating services to the MMRRC consortium and biomedical researchers. The announcement includes a requirement for the center’s close coordination with efforts to develop new approach methodologies (NAMs) that complement traditional animal-based research. These include cell culture, organoids, computational models, and microphysiological systems. Proposed activities should include collection and analysis of comparative information on the use of NAMs that enhance the predictive power of human disease models and support their integration with traditional models.
- Notice of Funding Opportunity: Resource-Related Research Projects for Development of Models and Related Materials for Studying Human Health and Diseases (R24 Clinical Trials Not Allowed)
ORIP encourages grant applications aimed at developing, characterizing, or improving research models for human health and diseases; developing biology-based new approach methodologies (NAMs) applicable to human health and diseases; or improving access to information about or generated from the use of models for human disease. The models, including NAMs, and related biological materials developed must be broadly applicable to the scientific interests of two or more NIH institutes or centers and must evaluate diseases and processes that impact multiple organ systems in alignment with ORIP’s NIH-wide mission and programs.
- Precision Model Centers Introductory Meeting
ORIP organized and presented at the Precision Model Centers Introductory Meeting on September 15, 2025. This virtual meeting included principal investigators and project leads of ORIP’s renewed U54 Division of Comparative Medicine (DCM) initiative, the Precision Model Centers Consortium. Program officials of the projects (DCM) and project scientists (Division of Construction and Instruments) attended the meeting, presented the plan for the new cycle, discussed collaborations, and planned future meetings.
- International Mouse Phenotyping Consortium Network Call
An ORIP staff member presented an NIH update on new approach methodologies (NAMs) and the use of animals in research at the International Mouse Phenotyping Consortium (IMPC) network call on August 12, 2025. The IMPC monthly call includes members of the IMPC, as well as NIH staff. ORIP’s presentation was devoted to the current NIH policies regarding use of animals in research, as well as NAM initiatives. Attendees discussed implementation of the policies and their potential effect on Knockout Mouse Project/IMPC activities.
- Cryopreservation Workshop, Session V: Long-Term Preservation Methods for Nonhuman Primate Models in Biomedical Research
ORIP hosted the Cryopreservation and Other Preservation Approaches for Animal Models Workshop to address topics related to cryopreservation and other preservation methods. Session V, held on July 15, 2025, focused on long-term preservation of nonhuman primate models for biomedical research. This session brought together experts in the field to discuss current state-of-the-art techniques, as well as challenges and barriers in the field. A summary of the workshop will be posted on the ORIP website.
Read more in the archive.
ORIP-Supported Research Highlights
- Conditional Dmd Ablation in Muscle and Brain Causes Profound Effects on Muscle Function and Neurobehavior
People with Duchenne muscular dystrophy (DMD) have skeletal and cardiopulmonary weakness caused by changes to the dystrophin protein, and up to one-third also are diagnosed on the autism spectrum. Researchers created an improved mouse model that allowed them to remove large gene isoforms (mRNA variations of the gene that may alter function) within the coding for dystrophin. The mouse Dmd gene has several isoforms that affect the skeletal muscle, heart, and brain. Researchers were able to define tissue-specific requirements of dystrophin in skeletal muscle during early and postnatal muscle growth and regeneration. They also observed some learning, cognitive, and social deficits in this 4- to-6-month-old male mouse model that are shared by other DMD mouse models. This increased understanding of how dystrophin loss affects people with DMD will help researchers develop gene therapies and treatment strategies.
- Exceptional Diversity of Allorecognition Receptors in a Nonvertebrate Chordate Reveals Principles of Innate Allelic Discrimination
Allorecognition—the ability to distinguish self from non-self—is found in many species and is the basis for many processes, such as mate choice, space competition, and immune function. Botryllus schlosseri is a marine invertebrate (a life form lacking a spine) that has many similarities to vertebrates in allorecognition genomic organization and signaling pathways. Researchers used B. schlosseri to investigate allorecognition and identified an unprecedented level of receptor diversity and adaptive ability in the alleles (alternative versions of a gene) used to determine compatibility. These results provide insight into signal processing and allorecognition processes across a broad range of animals.
- A Tandem Repeat Atlas for the Genome of Inbred Mouse Strains: A Genetic Variation Resource
Tandem repeats (TRs) are repetitive DNA sequences. TRs are a significant source of genetic variation in the human population, responsible for unique biomedical traits among individuals and more than 60 genetic diseases. Researchers used long-read sequencing and state-of-the-art computational programs to produce a database of more than 2 million TRs that cover 39 inbred mouse strains (males used). Results showed that there were important similarities and differences among species and that TR alleles (alternative versions of a gene) are important for genetic discovery. Analysis of two biomedical phenotypes (physical characteristics), which were characterized in inbred mouse strains more than 40 years ago, identified the genetic factors that can cause these phenotypes. This research is essential for characterizing the unique genetic variations that cause trait differences and advancing fundamental biological research and translational medicine.
- A Porcine Model of Fanconi Anemia
Fanconi anemia (FA) causes birth and developmental defects because of disrupted DNA repair. Without the ability to repair DNA damage, mutations continue to collect in the patient’s tissues, which leads to anemia, bone marrow failure, and cancer. Mouse and rat models for FA do not mimic the key clinical symptoms of FA, such as anemia. A pig model of FA could accurately mimic many of the clinical features seen in human patients because pigs have similar physiology and a relatively long lifespan. Researchers targeted the FANCA gene in domestic pigs. The FANCA porcine model (sex not stated) showed skeletal abnormalities, extreme sensitivity to agents that cause DNA crosslinks (a type of DNA damage), hematopoietic progenitor cell reduction, enlarged red blood cells, and reduced neutrophil (a type of immune cell) numbers in peripheral blood. Mitomycin C treatment resulted in a tenfold increase in chromosomal radials—where a segment of one chromosome breaks off and attaches to another, causing unbalanced rearrangements due to improper DNA repair—which is a diagnostic marker for FA in patients. This study shows that the FANCA porcine model is a promising preclinical model for developing strategies to prevent bone marrow failure and malignancies in FA patients.
- Long-Acting Lenacapavir Acts as an Effective Preexposure Prophylaxis in a SHIV Challenge Macaque Model
Preexposure prophylaxis (PrEP) is a form of medicine that protects a person from getting a disease rather than having to treat them after they get sick. Daily oral PrEP is an effective way to prevent new HIV infections, but it must be taken as instructed. PrEP that requires less-frequent doses would make it easier and more convenient to keep taking the medication and would reduce clinical visits. Using 3- to 5-year-old male rhesus macaques, researchers showed that a single dose of lenacapavir injected beneath the skin produced sustained levels of the drug in plasma. It also provided strong preventive activity against a high-dose simian-human immunodeficiency virus (SHIV) administered rectally. No drug resistance emerged, and SHIV infections occurred only when the drug level fell below the target needed for complete protection. These findings give researchers critical data about dosing intervals, protective concentrations, and the long-acting potential of lenacapavir. This knowledge will support lenacapavir’s progression to human HIV PrEP trials.
Read more in the archive.
