Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo

Lewis, Rowena S., Stephenson, Sarah E.M. and Ward, Alister 2006, Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo, Experimental hematology, vol. 34, no. 2, pp. 179-187.

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Title Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo
Author(s) Lewis, Rowena S.
Stephenson, Sarah E.M.
Ward, Alister
Journal name Experimental hematology
Volume number 34
Issue number 2
Start page 179
End page 187
Publisher Elsevier Inc.
Place of publication New York, N.Y.
Publication date 2006-02
ISSN 0301-472X
1873-2399
Summary Objective
Constitutive activation of Stat5 has been observed in a variety of malignancies, particularly myeloid leukemias. To directly investigate the in vivo consequences of Stat5 perturbation, we expressed constitutively active forms in zebrafish.
Methods
We generated mutants of the zebrafish stat5.1 protein (N646H, H298R/N714F, and N714F) based on previously identified constitutively active mutants of murine Stat5a. The in vitro properties of these mutants were determined using phosphorylation-specific antibodies and luciferase reporter assays, and their in vivo effects were analyzed through microinjection of zebrafish embryos.
Results
Two of these stat5.1 mutants (N646H and H298R/N714F) showed increased tyrosine phosphorylation and transactivation activity compared to the wild-type protein. Expression of either mutant led to a range of hematological perturbations, which were more pronounced for the H298R/N714F mutant. Interestingly, expression of wild-type also produced generally similar phenotypes. Further analysis showed that expression of the H298R/N714F mutant led to increased numbers of early and late myeloid cells, erythrocytes, and B cells. Some nonhematopoietic developmental perturbations were also observed, but these were equally prominent with wild-type or mutant forms.
Conclusion
These data implicate Stat5 activity as a direct critical regulator of hematological cell proliferation, suggesting a causal role for constitutively-active Stat5 in the etiology of hematological malignancies.

Language eng
Field of Research 110202 Haematology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2006, International Society for Experimental Hematology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30003928

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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