Programs and Activities Highlights
- Notice of Extension of the Expiration Date for RFA-OD-22-013, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24, Clinical Trials Not Allowed)
ORIP published a notice to extend the expiration date for RFA-OD-22-013, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24, Clinical Trials Not Allowed). RFA-OD-22-013 now expires on September 26, 2025. ORIP’s intent with this funding opportunity is to support resource-related research projects that are aimed at developing and characterizing new resources; improving existing resources; or acquiring deep understanding of a model system to improve the utilization, accessibility, and translational values of models to the research community.
- International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project Annual Fall Meeting
The International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project (KOMP) Annual Fall Meeting was held on September 15–16, 2024. An ORIP staff member monitored overall project progress and exchange of scientific knowledge of the international collaboration, contributed to the discussions, conducted an in-depth review of the data provided, and crafted meeting conclusions. The meeting conclusions were communicated to the NIH KOMP Working Group and ORIP and DPCPSI leadership.
- Czech Centre for Phenogenomics Conference 2024
An ORIP staff member represented the International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project at an international community phenotyping conference on September 17–18, 2024. He participated in discussions regarding the use of animal models for the development of preclinical drug testing pipelines, as well as genome editing therapeutics.
- ORIP Concept Clearance (Reissue): National Primate Research Centers Program
In light of the National Primate Research Centers (NPRCs) Program’s demonstrated success and the critical need to ensure national availability of nonhuman primate (NHP) resources, ORIP requested concept clearance from the Council of Councils on September 12, 2024, to continue its support for the program. The NPRCs Program complements and enables the missions of the other NIH institutes and centers by providing the animals, facilities, expertise, and resources required to enable NHP research in specific disease areas.
- Cryopreservation Workshop Session II: Cryopreservation and Development of Sustainable Germplasm Repositories for Aquatic Biomedical Models
The second session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held on September 9–10, 2024. Session II focused on the advancements and future needs of genetic resources of aquatic biomedical models, including zebrafish, Xenopus, Ambystoma, and Xiphophorus. The meeting featured three keynote talks and panel presentations by more than 36 panelists. The workshop participants discussed challenges associated with funding and training, the need for standardized protocols, and the benefits that universal data management systems and training hubs would provide.
Read more in the archive.
ORIP-Supported Research Highlights
- SIV Proviruses Seeded Later in Infection Are Harbored in Short-Lived CD4+ T Cells
HIV can stay dormant for years by mixing its genetic materials into immune cells, making it difficult to remove. It remains unclear which HIV-infected cells survive long term. This study used samples from simian immunodeficiency virus (SIV)–infected macaques (sex not specified) to examine how and when virus-infected cells become part of the long-lived reservoir. Researchers discovered that newer viral sequences were found in short-lived CD4+ T cells, and long-lived cells contained older, more genetically varied viruses. These results suggest that viruses from early infection persist in the long term, whereas newer infections remain in cells that die off quickly, providing insights on future HIV treatment strategies.
- Transplantation of Human Kidney Organoids Elicited a Robust Allogeneic Response in a Humanized Mouse Model
Kidney organoids are helping advance studies focused on kidney diseases. However, the use of kidney organoids in studies on tissue transplanted from one organism into another is not well explored. Researchers used a humanized mouse model (sex not specified) that contained a human immune system. Following the transplantation of kidney organoids into the humanized mice, researchers looked at the immune response at days 20 and 30. Results showed that transplantation of kidney organoids caused infiltration of immune cells and an increase in the number of T cells. This study provides a novel platform for bridging the gap between mouse and human studies, which may hasten the development of drugs that reduce tissue rejection in organ transplants.
- Caspase-11 Drives Macrophage Hyperinflammation in Models of Polg-Related Mitochondrial Disease
Mitochondria are the energy-producing organelles within cells. Mitochondrial diseases lead to chronic health impairments, which can be worsened by environmental exposures, including bacterial infections. Researchers used a mouse model (sex not specified) to study polymerase gamma (Polg)–related mitochondrial disease. They found that infection with the bacteria Pseudomonas aeruginosa causes macrophages (a type of immune cell) to have an increased response. The response happens through cytokine-mediated increases of caspase-11 and guanylate-binding proteins, which leads to lung inflammation. These findings will help scientists find targets to develop therapies to limit infection- and inflammation-related complications in mitochondrial diseases.
- Synaptic Dysregulation in a Mouse Model of GRIN2D Developmental and Epileptic Encephalopathy
Researchers studied a mutation in the GRIN2D gene that is linked to severe developmental delays and epilepsy in children. Using a mouse model (both sexes used), researchers showed that the mutation caused early-onset seizures, abnormal brain activity, and learning impairments. Functional analysis demonstrated increased synaptic activity, leading to heightened hippocampal excitability. These findings highlight how this mutation alters excitatory and inhibitory neuronal signaling in the brain. This work suggests that precision genetic therapy is a promising treatment strategy for patients with mutations in the GRIN2D gene.
- Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Mutation Reduces Endothelial TDP-43 and Causes Blood–Brain Barrier Defects
Mutations in the TARDBP gene are linked to neurodegenerative diseases, such as familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This study showed that the protein TDP-43 is reduced in brain endothelial cells of male and female mice with this mutation—leading to blood–brain barrier (BBB) disruption and causing inflammation, protein buildup, and cognitive issues—mimicking key features of neurodegeneration. These findings suggest that endothelial TDP-43 loss contributes directly to BBB breakdown and disease pathology in ALS-FTD.
Read more in the archive.
