PUBLICATION
Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.
- Authors
- Chi, Y., Huang, Z., Chen, Q., Xiong, X., Chen, K., Xu, J., Zhang, Y., Zhang, W.
- ID
- ZDB-PUB-180727-5
- Date
- 2018
- Source
- Open Biology 8(7): (Journal)
- Registered Authors
- Chi, Yali, Huang, Zhibin, Xiong, Xiaojie, Zhang, Wenqing, Zhang, Yiyue
- Keywords
- Runx1 mutation, immunodeficiency, lymphocyte, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis
- B-Lymphocytes/cytology
- B-Lymphocytes/immunology*
- Core Binding Factor Alpha 2 Subunit/deficiency
- Core Binding Factor Alpha 2 Subunit/genetics*
- Evolution, Molecular
- Immunoglobulins/genetics
- Immunoglobulins/metabolism
- Mutation
- T-Lymphocytes/cytology
- T-Lymphocytes/immunology*
- V(D)J Recombination
- Zebrafish/genetics*
- Zebrafish/immunology
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics*
- PubMed
- 30045885 Full text @ Open Biol.
Citation
Chi, Y., Huang, Z., Chen, Q., Xiong, X., Chen, K., Xu, J., Zhang, Y., Zhang, W. (2018) Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.. Open Biology. 8(7):.
Abstract
Transcription factor RUNX1 holds an integral role in multiple-lineage haematopoiesis and is implicated as a cofactor in V(D)J rearrangements during lymphocyte development. Runx1 deficiencies resulted in immaturity and reduction of lymphocytes in mice. In this study, we found that runx1W84X/W84X mutation led to the reduction and disordering of B cells, as well as the failure of V(D)J rearrangements in B cells but not T cells, resulting in antibody-inadequate-mediated immunodeficiency in adult zebrafish. By contrast, T cell development was not affected. The decreased number of B cells mainly results from excessive apoptosis in immature B cells. Disrupted B cell development results in runx1W84X/W84X mutants displaying a similar phenotype to common variable immunodeficiency-a primary immunodeficiency disease primarily characterized by frequent susceptibility to infection and deficient immune response, with marked reduction of antibody production of IgG, IgA and/or IgM. Our studies demonstrated an evolutionarily conserved function of runx1 in maturation and differentiation of B cells in adult zebrafish, which will serve as a valuable model for the study of immune deficiency diseases and their treatments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping