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

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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.

History

Journal

International Journal of Molecular Sciences

Volume

23

Issue

4

Article number

2385

Pagination

1 - 13

Publisher

MDPI

Location

Basel, Switzerland

ISSN

1661-6596

eISSN

1422-0067

Language

English

Publication classification

C1 Refereed article in a scholarly journal