Programs and Activities Highlights
- Access to Genetically Engineered Mouse Resources
During the 22nd Workshop on the Pathology of Mouse Models for Human Disease, an ORIP staff member presented on access to genetically engineered mouse resources. The workshop was held both virtually and in person from April 20–24, 2026, at St. Jude Children’s Research Hospital in Memphis, Tennessee. - ORIP Workshop: Cryopreservation and Other Preservation Approaches for Animal Models
The final session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held virtually on April 27, 2026. The session addressed cryopreservation and other methods for swine models in biomedical research. During the discussion, the workshop presenters and participants identified needs related to facility infrastructure and regional hubs, animal maintenance, technology advancements, automation strategies, protocol optimization, reagent creation, and training opportunities. A report will be available on the ORIP website at a later date. - INCLUDE Project: Exploratory/Developmental Research Awards for Down Syndrome (R21 Clinical Trial Not Allowed)
The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve the health and quality of life for individuals with Down syndrome. ORIP has signed onto this notice of funding opportunity, which invites researchers to submit applications for supporting new exploratory and developmental research projects that address critical needs for Down syndrome projects, as articulated in the INCLUDE Project objectives. - Notice of Funding Opportunity: Animal and Biological Material Resource Centers (P40 Clinical Trial Not Allowed)
This notice of funding opportunity (NOFO) encourages grant applications for Animal and Biological Material Resource Centers. These centers provide support for special colonies of laboratory animals and associated services, as well as other resources, such as informatics tools, reagents, cultures (cells, tissues, and organs), and genetic stocks that serve the biomedical research community in a variety of research areas on a local, regional, and national basis. Of special interest is a requirement for the Center to closely coordinate with efforts to develop new approach methodologies (NAMs) that complement traditional animal-based research. The Applied Research Component of the project should include studies to generate comparative data to increase applicability of NAMs and promote integration of the most predictive human disease models. The goal of projects supported by this NOFO is to provide research resources that facilitate the optimization and enhancement of scientific rigor, transparency, and experimental reproducibility of biomedical research. Proposed Animal and Biological Material Resource Centers must have broad application to multiple NIH institutes or centers (ICs) to align with ORIP’s NIH-wide mission. - International Mouse Phenotyping Consortium: Insights from the Past, Shaping the Future
The International Mouse Phenotyping Consortium (IMPC) meeting was held on January 22, 2026. An ORIP staff member chaired session 1, which included an update on IMPC production and phenotyping efforts to date. This virtual meeting focused on three pillars: the progress and achievements of IMPC to date; the program’s impact on basic and applied biomedical research, as well as understanding disease mechanisms and advancing human health; and the value and justification for continuing the Knockout Mouse Phenotyping Project (KOMP)/IMPC program, as well as suggestions for future directions and priorities. The goal of IMPC is to create a comprehensive catalog of mammalian gene function that is freely available and equally accessible to the global research community.
Read more in the archive.
ORIP-Supported Research Highlights
- In Vivo Base Editing Rescues Liver Pathophysiology and Peroxisome Dysfunction in a Mouse Model of Zellweger Spectrum Disorder
Zellweger spectrum disorder (ZSD) is caused by loss-of-function variations in any of 13 PEX genes that encode peroxins. Peroxins are required for the creation of peroxisomes (organelles in cells that convert hydrogen peroxide from normal cell processes into nontoxic products), which are critical for cell signaling and metabolism. ZSD often results in chronic conditions—including cirrhosis and hepatocellular carcinoma (liver cancer). Using a neonatal and 4-week-old mouse model (sex not stated) for ZSD, researchers tested a gene-editing strategy to correct the mutation. Results showed that 60% of the pathogenic allele (disease-causing version of a gene) was corrected in the liver. Researchers also tested the gene-editing strategy in patient-derived fibroblasts and observed more than 80% correction of the pathogenic allele. This correction prevented the buildup of toxic products in PEX-mutated peroxisomes. These findings support the use of gene editing to benefit individuals with ZSD and provide a foundation to create precision treatments for peroxisome disorders. - Adjuvant IL-15 Blockade Significantly Improves Survival in a CD28-Based Immunosuppression Protocol of Pig-to–Nonhuman Primate Renal Xenotransplantation
End-stage organ disease requires organ transplantation, but organ shortage remains the critical barrier for patients. Xenotransplantation (organ transfer from one organism to another) is a promising solution for this shortage. In a previous study, researchers identified a specific immune cell—natural killer (NK) cells—in rejected xenografts. Using a swine-to–nonhuman primate model for xenotransplantation (sex not stated), researchers showed that adding adjuvant αIL-15—an agent that reduces NK cells—to the immunosuppressive routine (drugs that decrease the immune response and chance of organ rejection) significantly increased xenograft survival and function. Results also showed that adjuvant αIL-15 shifted NK cells to a phenotype (physical characteristics) that lacked CD16 and CD56 expression. These findings support the use of an NK cell-targeted therapy to improve xenograft outcomes. - MIC-Drop-seq: Scalable Single-Cell Phenotyping of Mutant Vertebrate Embryos
Pooled perturbation screens (altering many genes at once with a gene-editing technique) can uncover regulatory networks, but it is difficult to scale this technique for large screens in animal models. In this study, researchers show the utility of MIC-Drop-seq to address the challenges with large-scale screens. MIC-Drop-seq is a technique that combines gene disruption, using CRISPR (a type of gene-editing technique), with single-cell RNA sequencing (a method to identify all the RNA molecules in a cell). Using MIC-Drop-seq with zebrafish embryos (sex not stated), researchers showed that loss of function mutations in 50 transcription factors (proteins that control the activity of genes) cause gene expression and cell number changes across 74 cell types. These results uncover several new roles for transcription factors in controlling embryonic development. This study emphasizes the importance of large-scale screens to understand how changes to one cell type influence the development of other cell types. MIC-Drop-seq will be useful for exploring gene networks that affect development. - EpicTope: Predicting and Validating Non-disruptive Epitope Tagging Sites
Epitope (a specific part of the molecule that an antibody recognizes) tagging is an in vivo (done within an organism) technique used to label, track, and purify proteins of interest. In this study, researchers develop a computation modeling tool—EpicTope—to identify the amino acid (building blocks of a protein) positions that are ideal for epitope labeling. The tool scores suitability based on many factors—including secondary (an intermediate form before a protein takes on its 3D structure) and tertiary (3D-folded) protein structure—to identify locations on the protein where adding an epitope would minimize disruptions to the protein’s function. Using 3‑month-old to 1.5-year-old zebrafish (sex not stated), researchers validated EpicTope-identified epitope tag insertion sites for two proteins, SMAD5 and HDAC1. SMAD5- and HDAC1-tagged proteins rescued expression levels in mutant zebrafish embryos. Results also showed that these tagged proteins can be detected with standard laboratory techniques. These findings support EpicTope as an effective tool for identifying sites for epitope tags. - Dominant Effects of the Immediate Environment on the Gut Microbiome of Mice Used in Biomedical Research
Genetically engineered mouse (GEM) models are vital for studying gene function and the effects of environmental factors in biological systems. The microbiome (the collection of microbes found in the body) of GEM models significantly influences model phenotypes (physical characteristics) and thus represents a possible source of poor reproducibility. Researchers collected fecal samples from 275 unique GEM models at 84 different research institutions. These research institutions were located across 34 U.S. states and 7 other countries. Results showed that the laboratory environment was the main factor in shaping the microbiome, and beta-diversity similarities were observed. A surprisingly high prevalence and amount of Helicobacter species was observed in the GEM model microbiomes. This highlights the importance of collecting fecal samples in phenotyping studies to understand how the microbiome affects the results.
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