ArticleDiabetes2010
Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
- Beyond the blood-brain barrier: humanised mice, the missing link in glioblastoma research.Oncogene · 2026Review
- Testing the capacity of humanized immune system mice to induce a protective antibody response against the Lyme disease pathogen.Microbiology spectrum · 2026Article
- The IsletTester Mouse: An Immunodeficient Model With Stable Hyperglycemia for the Study of Human Islets.Diabetes · 2025Article
- A Novel Immunodeficient Hyperglycemic Mouse Carrying the Ins1 Akita Mutation for Xenogeneic Islet Cell Transplantation.Transplantation · 2025Article
- Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.Nature reviews. Endocrinology · 2025Review
- Diabetes-associated breast cancer is molecularly distinct and shows a DNA damage repair deficiency.JCI insight · 2023Article
- Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.Science advances · 2023Article
- NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.Journal of leukocyte biology · 2023Article
- Experimental mouse models for translational human cancer research.Frontiers in immunology · 2023Review
- Enhanced development of functional human NK cells in NOD-scid-IL2rgFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.Biomaterials · 2022Article
- Development of a novel human CD147 knock-in NSG mouse model to test SARS-CoV-2 viral infection.Cell & bioscience · 2022Article
- Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research.Journal of neuropathology and experimental neurology · 2022Review
- Development of a Novel Human CD147 Knock-in NSG Mouse Model to Test SARS-CoV-2 Viral Infection.Research square · 2022Article
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Mouse models and human islet transplantation sites for intravital imaging.Frontiers in endocrinology · 2022Review
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- Current Status, Barriers, and Future Directions for Humanized Mouse Models to Evaluate Stem Cell-Based Islet Cell Transplant.Advances in experimental medicine and biology · 2022Article
- Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses.Research square · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTo create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system. RESEARCH DESIGN AND
methodsWe backcrossed the Ins2(Akita) mutation onto the NOD-Rag1(null) IL2rgamma(null) strain and determined 1) the spontaneous development of hyperglycemia, 2) the ability of human islets, mouse islets, and dissociated mouse islet cells to restore euglycemia, 3) the generation of a human immune system following engraftment of human hematopoietic stem cells, and 4) the ability of the humanized mice to reject human islet allografts.
resultsWe confirmed the defects in innate and adaptive immunity and the spontaneous development of hyperglycemia conferred by the IL2rgamma(null), Rag1(null), and Ins2(Akita) genes in NOD-Rag1(null) IL2rgamma(null) Ins2(Akita) (NRG-Akita) mice. Mouse and human islets restored NRG-Akita mice to normoglycemia. Insulin-positive cells in dissociated mouse islets, required to restore euglycemia in chemically diabetic NOD-scid IL2rgamma(null) and spontaneously diabetic NRG-Akita mice, were quantified following transplantation via the intrapancreatic and subrenal routes. Engraftment of human hematopoietic stem cells in newborn NRG-Akita and NRG mice resulted in equivalent human immune system development in a normoglycemic or chronically hyperglycemic environment, with >50% of engrafted NRG-Akita mice capable of rejecting human islet allografts.
conclusionsNRG-Akita mice provide a model system for validation of the function of human islets and human adult stem cell, embryonic stem cell, or induced pluripotent stem cell-derived beta-cells in the absence or presence of an alloreactive human immune system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.