PUBLICATION
Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation
- Authors
- Basheer, F., Lee, E., Liongue, C., Ward, A.C.
- ID
- ZDB-PUB-221028-19
- Date
- 2022
- Source
- Biomolecules 12(10): (Journal)
- Registered Authors
- Liongue, Clifford, Ward, Alister C.
- Keywords
- JAK3, SCID, immunodeficiency, leukemia, lymphoid cells, zebrafish
- MeSH Terms
-
- Adult
- Animals
- Humans
- Janus Kinase 3/genetics
- Mutation
- Receptors, Interleukin-2
- Severe Combined Immunodeficiency*/genetics
- Signal Transduction
- Zebrafish/genetics
- PubMed
- 36291730 Full text @ Biomolecules
Citation
Basheer, F., Lee, E., Liongue, C., Ward, A.C. (2022) Zebrafish Model of Severe Combined Immunodeficiency (SCID) Due to JAK3 Mutation. Biomolecules. 12(10):.
Abstract
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 jak3 created mutants similar to those observed in human SCID. Homozygous jak3 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping