Generation and Characterization of a Zebrafish IL-2Rγc SCID Model.

Robert Sertori, Realla Jones, Faiza Basheer, Leni Rivera, Samantha Dawson, Stella Loke, Somayyeh Heidary, Amardeep Dhillon, Clifford Liongue, Alister C Ward

International journal of molecular sciences 2022 Feb 21

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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.

Citation

Robert Sertori, Realla Jones, Faiza Basheer, Leni Rivera, Samantha Dawson, Stella Loke, Somayyeh Heidary, Amardeep Dhillon, Clifford Liongue, Alister C Ward. Generation and Characterization of a Zebrafish IL-2Rγc SCID Model. International journal of molecular sciences. 2022 Feb 21;23(4)