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, doi: 10.1016/j.exphem.2009.08.008. Attached Files Name Description MIMEType Size Downloads 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. orcid.org/0000-0001-7945-7975 Liongue, Clifford orcid.org/0000-0002-1646-4905 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 DOI 10.1016/j.exphem.2009.08.008 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 Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Wed, 03 Feb 2010, 14:03:18 EST Thu, 04 Feb 2010, 08:16:53 EST Thu, 04 Feb 2010, 08:19:16 EST Fri, 05 Feb 2010, 10:17:53 EST Thu, 12 May 2011, 12:42:35 EST Mon, 16 Jun 2014, 14:17:28 EST Fri, 22 Aug 2014, 13:59:30 EST Fri, 17 Oct 2014, 10:04:06 EST Filtered Full Citation counts:   Cited 20 times in TR Web of Science Cited 22 times in Scopus Search Google Scholar Access Statistics: 1173 Abstract Views, 2 File Downloads  -  Detailed Statistics Created: Wed, 03 Feb 2010, 14:03:16 EST by Sally Morrigan