PUBLICATION
Generation and Characterization of a Zebrafish IL-2Rγc SCID Model
- Authors
- Sertori, R., Jones, R., Basheer, F., Rivera, L., Dawson, S., Loke, S., Heidary, S., Dhillon, A., Liongue, C., Ward, A.C.
- ID
- ZDB-PUB-220227-11
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(4): (Journal)
- Registered Authors
- Liongue, Clifford, Ward, Alister C.
- Keywords
- IL-2Rγc, immunodeficiency, microbiota, xenotransplantation, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Base Sequence
- Gastrointestinal Microbiome/physiology
- Interleukin Receptor Common gamma Subunit
- Killer Cells, Natural/metabolism
- Lymphopoiesis/physiology
- Models, Animal
- Phenotype
- Severe Combined Immunodeficiency/metabolism*
- T-Lymphocytes/metabolism
- Zebrafish/metabolism*
- PubMed
- 35216498 Full text @ Int. J. Mol. Sci.
Citation
Sertori, R., Jones, R., Basheer, F., Rivera, L., Dawson, S., Loke, S., Heidary, S., Dhillon, A., Liongue, C., Ward, A.C. (2022) Generation and Characterization of a Zebrafish IL-2Rγc SCID Model. International Journal of Molecular Sciences. 23(4):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping