International Journal of Molecular Sciences · 2022 · 16 citations · 36 references
Life SciencesGeneticsImmunologyGenome EditingImmunogeneticsInnate ImmunityCytokine BiologyImmune Cell SignalingImmune Gene RegulationImmunological Disease ModelsInnate Lymphoid CellsT Cell BiologyGain-of-function AllelesIl2rg DeficiencyImmune Cell Gene EditingImmune Receptor Signaling ComplexesInterleukin-2 Receptor Gamma Chain DeficiencyIntestinal Microbiota EffectsKnockout Zebrafish ModelsLoss-of-function Alleles
The 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.
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A severe combined immunodeficiency mutation in the mouse
Gayle C. Bosma, R. Philip Custer, Melvin J. Bosma · Nature · 1983 · 2.2K citations
Life Sciences, Genetics, Immunology +12