Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation
JAK3 is principally activated by members of the interleukin-2 receptor family and plays an essential role in lymphoid development, with inactivating JAK3 mutations causing autosomal-recessive severe combined immunodeficiency (SCID). This study aimed to generate an equivalent zebrafish model of SCID...
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MDPI AG
2022-10-01
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Online Access: | https://www.mdpi.com/2218-273X/12/10/1521 |
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author | Faiza Basheer Effie Lee Clifford Liongue Alister C. Ward |
author_facet | Faiza Basheer Effie Lee Clifford Liongue Alister C. Ward |
author_sort | Faiza Basheer |
collection | DOAJ |
description | JAK3 is principally activated by members of the interleukin-2 receptor family and plays an essential role in lymphoid development, with inactivating JAK3 mutations causing autosomal-recessive severe combined immunodeficiency (SCID). This study aimed to generate an equivalent zebrafish model of SCID and to characterize the model across the life-course. Genome editing of zebrafish <i>jak3</i> created mutants similar to those observed in human SCID. Homozygous <i>jak3</i> mutants showed reduced embryonic T lymphopoiesis that continued through the larval stage and into adulthood, with B cell maturation and adult NK cells also reduced and neutrophils impacted. Mutant fish were susceptible to lymphoid leukemia. This model has many of the hallmarks of human SCID resulting from inactivating JAK3 mutations and will be useful for a variety of pre-clinical applications. |
first_indexed | 2024-03-09T20:36:08Z |
format | Article |
id | doaj.art-9670c623cdb84cd39406a20d7c8552ce |
institution | Directory Open Access Journal |
issn | 2218-273X |
language | English |
last_indexed | 2024-03-09T20:36:08Z |
publishDate | 2022-10-01 |
publisher | MDPI AG |
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series | Biomolecules |
spelling | doaj.art-9670c623cdb84cd39406a20d7c8552ce2023-11-23T23:09:59ZengMDPI AGBiomolecules2218-273X2022-10-011210152110.3390/biom12101521Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 MutationFaiza Basheer0Effie Lee1Clifford Liongue2Alister C. Ward3School of Medicine, Deakin University, Waurn Ponds, Geelong, VIC 3216, AustraliaGribbles Veterinary Pathology, Glenside, SA 5065, AustraliaSchool of Medicine, Deakin University, Waurn Ponds, Geelong, VIC 3216, AustraliaSchool of Medicine, Deakin University, Waurn Ponds, Geelong, VIC 3216, AustraliaJAK3 is principally activated by members of the interleukin-2 receptor family and plays an essential role in lymphoid development, with inactivating JAK3 mutations causing autosomal-recessive severe combined immunodeficiency (SCID). This study aimed to generate an equivalent zebrafish model of SCID and to characterize the model across the life-course. Genome editing of zebrafish <i>jak3</i> created mutants similar to those observed in human SCID. Homozygous <i>jak3</i> mutants showed reduced embryonic T lymphopoiesis that continued through the larval stage and into adulthood, with B cell maturation and adult NK cells also reduced and neutrophils impacted. Mutant fish were susceptible to lymphoid leukemia. This model has many of the hallmarks of human SCID resulting from inactivating JAK3 mutations and will be useful for a variety of pre-clinical applications.https://www.mdpi.com/2218-273X/12/10/1521JAK3immunodeficiencySCIDlymphoid cellsleukemiazebrafish |
spellingShingle | Faiza Basheer Effie Lee Clifford Liongue Alister C. Ward Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation Biomolecules JAK3 immunodeficiency SCID lymphoid cells leukemia zebrafish |
title | Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation |
title_full | Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation |
title_fullStr | Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation |
title_full_unstemmed | Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation |
title_short | Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation |
title_sort | zebrafish model of severe combined immunodeficiency scid due to jak3 mutation |
topic | JAK3 immunodeficiency SCID lymphoid cells leukemia zebrafish |
url | https://www.mdpi.com/2218-273X/12/10/1521 |
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