Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo
Data(s) |
01/02/2006
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Resumo |
<b>Objective</b><br />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.<br /><b>Methods</b><br />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.<br /><b>Results</b><br />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.<br /><b>Conclusion</b><br />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.<br /><br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
Elsevier Inc. |
Relação |
http://dro.deakin.edu.au/eserv/DU:30003928/n20061322.pdf http://dx.doi.org/10.1016/j.exphem.2005.11.003 |
Direitos |
2006, International Society for Experimental Hematology |
Tipo |
Journal Article |