ArticleScientific reports2016
Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 99 citations in OpenAlex.
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- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Enhancing the specificity of gene editing outcomes by using Cas9 variants in porcine embryos.Journal of animal science · 2026Article
- Evolutionary insights and structural characterization guide the development of RAG1/RAG2-deficient swine models for immunological research.Frontiers in immunology · 2026Article
- Analysis of Cytosine Base Editors in Bovine Zygotes: Efficiency and Editing Window Characterization Through Targeting theCurrent issues in molecular biology · 2025Article
- Fetal bone engraftment reconstitutes the immune system in pigs with severe combined immunodeficiency.Lab animal · 2024Article
- Virus Shedding and Diarrhea: A Review of Human Norovirus Genogroup II Infection in Gnotobiotic Pigs.Viruses · 2024Review
- Generation of RAG2 Knockout Immune-Deficient Miniature Pigs.Animals : an open access journal from MDPI · 2024Article
- Novel off-Targeting Events Identified after Genome Wide Analysis of CRISPR-Cas Edited Pigs.The CRISPR journal · 2024Article
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- Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy.Ultrasound in medicine & biology · 2023Article
- The history, use, and challenges of therapeutic somatic cell and germline gene editing.Fertility and sterility · 2023Review
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- Inactivation of growth differentiation factor 9 blocks folliculogenesis in pigs†.Biology of reproduction · 2023Article
- Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection.Viruses · 2022Article
- In Vivo Modeling of Human Breast Cancer Using Cell Line and Patient-Derived Xenografts.Journal of mammary gland biology and neoplasia · 2022Review
- Advances in pig models of human diseases.Animal models and experimental medicine · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Application of genetically engineered (GE) large animals carrying multi-allelic modifications has been hampered by low efficiency in production and extended gestation period compared to rodents. Here, we rapidly generated RAG2/IL2RG double knockout pigs using direct injection of CRISPR/Cas9 system into developing embryos. RAG2/IL2RG deficient pigs were immunodeficient, characterized by depletion of lymphocytes and either absence of or structurally abnormal immune organs. Pigs were maintained in gnotobiotic facility and evaluated for human norovirus (HuNoV) infection. HuNoV shedding lasted for 16 days in wild type pigs, compared to 27 days (until the end of trials) in RAG2/IL2RG deficient pigs. Additionally, higher HuNoV titers were detected in intestinal tissues and contents and in blood, indicating increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs and the importance of lymphocytes in HuNoV clearance. These results suggest that GE immunodeficient gnotobiotic pigs serve as a novel model for biomedical research and will facilitate HuNoV studies.
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Registered trials
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