PUBLICATION
Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte-specific reporter line in zebrafish
- Authors
- Lin, Q., Zhang, Y., Zhou, R., Zheng, Y., Zhao, L., Huang, M., Zhang, X., Leung, A.Y., Zhang, W., Zhang, Y.
- ID
- ZDB-PUB-161105-10
- Date
- 2017
- Source
- Leukemia 31(5): 1206-1216 (Journal)
- Registered Authors
- Lin, Qing, Zhang, Yangping, Zhang, Yiyue, Zhou, Riyang
- Keywords
- none
- MeSH Terms
-
- Animals
- Blood Platelets/pathology
- Disease Models, Animal*
- Genes, Reporter
- Green Fluorescent Proteins/genetics
- Humans
- Janus Kinase 2/metabolism
- Receptors, Thrombopoietin/genetics*
- Receptors, Thrombopoietin/metabolism
- Signal Transduction
- Thrombocytopenia/pathology*
- Thrombopoietin/metabolism
- Zebrafish*
- PubMed
- 27811851 Full text @ Leukemia
Citation
Lin, Q., Zhang, Y., Zhou, R., Zheng, Y., Zhao, L., Huang, M., Zhang, X., Leung, A.Y., Zhang, W., Zhang, Y. (2017) Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte-specific reporter line in zebrafish. Leukemia. 31(5):1206-1216.
Abstract
Mutations in the human myeloproliferative leukemia protein gene (MPL) are known to cause congenital amegakaryocytic thrombocytopenia (CAMT). The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. Here, by using transcription activator-like effect or nucleases (TALEN) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl leaded to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult HSPCs. We further demonstrated that thrombocytopenia in mpl mutant zebrafish was caused by impaired Tpo/Mpl/Jak2 signaling, resulting in reduced proliferation of thrombocyte precursors. These results indicate that mpl mutant zebrafish develop thrombocytopenia resembling the human CAMT. To fully utilize zebrafish to study thrombocyte biology and thrombocytopenia disorders, we generated a transgenic reporter line Tg(mpl:eGFP)smu4, in which green fluorescent protein (GFP) expression was driven by the mpl promoter. Detailed characterization of Tg(mpl:eGFP)smu4 fish confirmed that the thrombocyte lineage was specifically marked by GFP expression. In conclusion, we generated the first transmissible congenital thrombocytopenia zebrafish model mimicking human CAMT and a thrombocyte-specific transgenic line. Together with Tg(mpl:eGFP)smu4, mpl mutant zebrafish provide a useful tool for drug screening and study of thrombocytopoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping