A novel zebrafish jak2a V581F model shared features of human JAK2 V617F polycythemia vera

Ma, Alvin C. H., Fan, August, Ward, Alister C., Liongue, Clifford, Lewis, Rowena S., Cheng, Suk H., Chan, P. K., Yip, Sze-Fai, Liang, Raymond and Leung, Anskar Y. H. 2009, A novel zebrafish jak2a V581F model shared features of human JAK2 V617F polycythemia vera, Experimental hematology, vol. 37, no. 12, pp. 1379-1386.

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Title A novel zebrafish jak2a V581F model shared features of human JAK2 V617F polycythemia vera
Author(s) Ma, Alvin C. H.
Fan, August
Ward, Alister C.
Liongue, Clifford
Lewis, Rowena S.
Cheng, Suk H.
Chan, P. K.
Yip, Sze-Fai
Liang, Raymond
Leung, Anskar Y. H.
Journal name Experimental hematology
Volume number 37
Issue number 12
Start page 1379
End page 1386
Total pages 8
Publisher Elsevier B.V.
Place of publication Amsterdam, The Netherlands
Publication date 2009-12
ISSN 0301-472X
1873-2399
Summary Objective : The Janus kinase 2 (JAK2) is important for embryonic primitive hematopoiesis. A gain-of-function JAK2 (JAK2V617F) mutation in human is pathogenetically linked to polycythemia vera (PV). In this study, we generated a zebrafish ortholog of human JAK2V617F (referred herewith jak2aV581F) by site-directed mutagenesis and examined its relevance as a model of human PV.

Materials and Methods : Zebrafish embryos at one-cell stage were injected with jak2aV581F mRNA (200pg/embryo). In some experiments, the embryos were treated with a specific JAK2 inhibitor, TG101209. The effects of jak2a stimulation on hematopoiesis, jak/stat signaling, and erythropoietin signaling were evaluated at 18-somites.

Results : Injection with jak2aV581F mRNA significantly increased erythropoiesis, as enumerated by flow cytometry based on gfp+ population in dissociated Tg(gata1:gfp) embryos. The response was reduced by stat5.1 morpholino coinjection (control: 4.37% ± 0.08%; jak2aV581F injected: 5.71% ± 0.07%, coinjecting jak2aV581F mRNA and stat5.1 morpholino: 4.66% ± 0.13%; p < 0.01). jak2aV581F mRNA also upregulated gata1 (1.83 ± 0.08 fold; p = 0.005), embryonic α-hemoglobin (1.61 ± 0.12 fold; p = 0.049), and β-hemoglobin gene expression (1.65 ± 0.13–fold; p = 0.026) and increased stat5 phosphorylation. These responses were also ameliorated by stat5.1 morpholino coinjection or treatment with a specific JAK2 inhibitor, TG101209. jak2aV581F mRNA significantly reduced erythropoietin gene (0.24 ± 0.03 fold; p = 0.006) and protein expression (control: 0.633 ± 0.11; jak2aV581F mRNA: 0.222 ± 0.07 mIU/mL; p = 0.019).

Conclusion : The zebrafish jak2aV581F model shared many features with human PV and might provide us with mechanistic insights of this disease.
Language eng
Field of Research 110707 Innate Immunity
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2009, ISEH
Persistent URL http://hdl.handle.net/10536/DRO/DU:30022878

Document type: Journal Article
Collection: School of Medicine
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