Journal
JOURNAL OF IMMUNOLOGY
Volume 193, Issue 11, Pages 5751-5757Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402059
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Funding
- Lung Biotechnology, LLC
- Indiana University Health Transplant Institute
- Indiana University Health
- Research Facilities Improvement Program Grant from the National Center for Research Resources [C06RR10601-01]
- National Institutes of Health
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Pigs are emerging as important large animal models for biomedical research, and they may represent a source of organs for xenotransplantation. The MHC is pivotal to the function of the immune system in health and disease, and it is particularly important in infection and transplant rejection. Pigs deficient in class I MHC could serve as important reagents to study viral immunity as well as allograft and xenograft rejection. In this study, we report the creation and characterization of class IMHC knockout pigs using the Cas9 nuclease and guide RNAs. Pig fetal fibroblasts were genetically engineered using Cas9 and guide RNAs, and class I MHC 2 cells were then used as nuclear donors for somatic cell nuclear transfer. We produced three piglets devoid of all cell surface class I proteins. Although these animals have reduced levels of CD4(-) CD8(+)T cells in peripheral blood, the pigs appear healthy and are developing normally. These pigs are a promising reagent for immunological research.
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