ward-generationcharacterization-2022.pdf (4.52 MB)
Generation and Characterization of a Zebrafish IL-2Rγc SCID Model
journal contribution
posted on 2022-01-01, 00:00 authored by Robert Sertori, Realla Maree Jones, Faiza BasheerFaiza Basheer, Leni RiveraLeni Rivera, Samantha DawsonSamantha Dawson, Stella LokeStella Loke, Somayyeh Heidary, Amardeep DhillonAmardeep Dhillon, Clifford LiongueClifford Liongue, Alister WardAlister WardThe IL-2 family of cytokines act via receptor complexes that share the interleukin-2 receptor gamma common (IL-2Rγc) chain to play key roles in lymphopoiesis. Inactivating IL-2Rγc mutations results in severe combined immunodeficiency (SCID) in humans and other species. This study sought to generate an equivalent zebrafish SCID model. The zebrafish il2rga gene was targeted for genome editing using TALENs and presumed loss-of-function alleles analyzed with respect to immune cell development and impacts on intestinal microbiota and tumor immunity. Knockout of zebrafish Il-2rγc.a resulted in a SCID phenotype, including a significant reduction in T cells, with NK cells also impacted. This resulted in dysregulated intestinal microbiota and defective immunity to tumor xenotransplants. Collectively, this establishes a useful zebrafish SCID model.
History
Journal
International Journal of Molecular SciencesVolume
23Issue
4Article number
2385Pagination
1 - 13Publisher
MDPILocation
Basel, SwitzerlandPublisher DOI
Link to full text
ISSN
1661-6596eISSN
1422-0067Language
EnglishPublication classification
C1 Refereed article in a scholarly journalUsage metrics
Categories
Keywords
Biochemistry & Molecular BiologyChemistryChemistry, MultidisciplinaryGENETIC-EVIDENCEIL-2R gamma cimmunodeficiencyLife Sciences & BiomedicinemicrobiotaMUTATIONPhysical SciencesRAG2Science & TechnologySEVERE COMBINED IMMUNODEFICIENCYT-CELL DEVELOPMENTTRANSPLANTATIONxenotransplantationzebrafishIL-2RγcGenetics
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