The role of jak2a in zebrafish hematopoiesis

Ma, Alvin C. H., Ward, Alister, Liang, Raymond and Leung, Anskar Y. H. 2007, The role of jak2a in zebrafish hematopoiesis, Blood, vol. 110, no. 6, pp. 1824-1830.

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Title The role of jak2a in zebrafish hematopoiesis
Author(s) Ma, Alvin C. H.
Ward, Alister
Liang, Raymond
Leung, Anskar Y. H.
Journal name Blood
Volume number 110
Issue number 6
Start page 1824
End page 1830
Publisher American Society of Hematology
Place of publication Washington, D.C.
Publication date 2007-09-15
ISSN 0006-4971
1528-0020
Summary Janus kinase 2 (Jak2) transduces signals from hematopoietic cytokines, and a gain-of-function mutation (Jak2617V>F) is associated with myeloproliferative diseases, particularly polycythemia vera. In this study, we examined the role of jak2a in zebrafish embryos in knock-down and overexpression studies using morpholinos (MOs) targeting the 5' untranslated region (UTR) (jak2aUTR-MO) and splice-site junction (jak2aSS-MO) of jak2a, a Jak inhibitor AG490 and a constitutive-active form of jak2a (jak2aca). At 18 and 24 hours after fertilization (hpf), jak2a is expressed predominantly in the intermediate cell mass (ICM; site of primitive hematopoiesis) of wild-type and chordin morphant embryos (characterized by expansion of ICM). Both jak2a MOs and AG490 reduced gata1+ (erythroid) cells in Tg(gata1:GFP) embryos, signal transducer and activation of transcription 5 (stat5) phosphorylation, and gene expression associated with early progenitors (scl and lmo2) and erythroid (gata1, he1 and ßhe1) and myeloid (spi1 [early] and mpo [late]) lineages. The chordin morphant is associated with increased stat5 phosphorylation, and both jak2a MOs and treatment with AG490 significantly ameliorated ICM expansion and hematopoietic gene up-regulation in these embryos. Injection of plasmid encoding jak2aca significantly increased erythropoiesis and expression of gata1, he1 and ßhe1, spi1, mpo, and l-plastin. In conclusion, zebrafish jak2a is involved in primitive hematopoiesis under normal and deregulated conditions.
Language eng
Field of Research 110202 Haematology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, The American Society of Hematology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007511

Document type: Journal Article
Collection: School of Medicine
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