Progress on Theme 1: Animal Models to Advance the Study of Human Disease

Programs and Activities Highlights

  • Grassroots Efforts to End Structural Racism Throughout the U.S. National Institutes of Health
    An open letter by NIH staff to the Director of the NIH helped to catalyze the NIH UNITE Initiative for Ending Structural Racism. ORIP staff participated in these grassroots efforts, as well as in the UNITE Initiative, to lead change within the NIH and the biomedical research ecosystem.

  • Severe Combined Immunodeficient Pig Models
    ORIP supports development of immunodeficient swine research models and resources to enable biomedical research on a wide range of human diseases. Two ORIP staff members served as panelists at the January 2022 virtual meeting, “Severe Combined Immunodeficient (SCID) Pig Models: Industry and Academia’s Needs.” The panel discussed the need for novel SCID pig models in various fields, such as stem cell therapy, regenerative medicine, cancer therapeutics, and organ transplantation. In addition to funding the National Swine Resource and Research Center, ORIP is supporting two projects focusing on improvement of SCID pigs with natural mutation or creating new mutants using state-of-the-art technologies.

  • ORIP 2021–2022 Resource and Research Centers
    ORIP supports 97 resource and research centers that develop animal models of human biology and disease. These centers develop, characterize, house, cryopreserve, and distribute both wild-type reference strains of animals, as well as mutant and genetically modified strains.
  • ORIP’s Rapid Response to the COVID-19 Pandemic
    ORIP issued administrative supplements to many of its research resource centers in 2021 to support the development of new animal models and other resources specifically designed to facilitate research on SARS-CoV-2 or to support research projects related to COVID-19.
  • ORIP Workshop: Validation of Animal Models and Tools for Biomedical Research
    ORIP—in collaboration with the National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke; and National Institute on Aging—held a series of virtual workshops between November 2020 and January 2021 to discuss the status and needs regarding the validation and rigor/reproducibility of animal models used in biomedical research.

Read more in the archive.

ORIP-Supported Research Highlights

  • Genetic Control of the Pluripotency Epigenome Determines Differentiation Bias in Mouse Embryonic Stem Cells
    Embryonic stem cells (ESCs) show an unlimited capacity for self-renewal and the ability to become any cell type in the body. Yet mechanisms for variation of ESCs from genetically diverse individuals remain largely unknown. Investigators studied regulation of cell state transitions in mouse ESCs derived from genetically diverse mouse strains and found differences in developmental potential of mouse ESCs in vitro. Recent experiments have shown that differences in cell-fate choice during development may be critical in predisposing individuals to complex diseases due to underlying differences in cell-type composition.
  • Blastocyst Development after Fertilization with In Vitro Spermatids Derived from Nonhuman Primate Embryonic Stem Cells
    Researchers investigated whether functional spermatids (immature forms of sperm cells) can be derived in vitro from nonhuman primate pluripotent stem cells. Rhesus macaque pluripotent stem cells were differentiated into spermatogenic germ cell linages and matured in vitro to form spermatids that were capable of fertilizing oocytes (female or germ cells involved in reproduction) by injection. Successful in vitro preimplantation embryo development was observed in approximately 12% of zygotes. The data suggest potential mechanisms to address male infertility.
  • Natural Disaster and Immunological Aging in a Nonhuman Primate
    Survivors of weather-related disasters exhibit early onset of age-related diseases. Investigators examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in age-matched, cross-sectional samples from free-ranging rhesus macaques living on an isolated island. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated protein regulation networks, and greater expression of inflammatory immune cell–specific marker genes. These findings illuminate how natural disasters might become biologically embedded and contribute to earlier onset of disease and death.
  • New Resources for the Drosophila 4th Chromosome: FRT101F Enabled Mitotic Clones and Bloom syndrome helicase Enabled Meiotic Recombination
    Seventy percent of the genes on the 4th chromosome of Drosophila melanogaster have human homologs that have a disease association. Yet, this chromosome is difficult to study because it lacks mitotic and meiotic recombination. Investigators developed technologies and stocks as a resource for the community, which enable genetic analysis of mutations on the 4th chromosome.
  • The Pigtail Macaque (Macaca nemestrina) Model of COVID-19 Reproduces Diverse Clinical Outcomes and Reveals New and Complex Signatures of Disease
    Animal models that reproduce clinical outcomes of human COVID-19 disease are critical for understanding SARS-CoV-2 viral and immune dynamics. Investigators demonstrate that pigtail macaques recapitulate important features of COVID-19 and reveal new immune and viral dynamics of SARS-CoV-2 infection.

Read more in the archive.

Last updated: 06-09-2022