Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct

Ishtiaq Ahmed, A. S., Xiong, Feng, Pang, Shao-Chen, He, Mu-Dan, Waters, Michael J., Zhu, Zuo-Yan and Sun, Yong-Hua (2011) Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct. Transgenic Research, 20 3: 557-567. doi:10.1007/s11248-010-9439-9


Author Ishtiaq Ahmed, A. S.
Xiong, Feng
Pang, Shao-Chen
He, Mu-Dan
Waters, Michael J.
Zhu, Zuo-Yan
Sun, Yong-Hua
Title Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct
Journal name Transgenic Research   Check publisher's open access policy
ISSN 0962-8819
Publication date 2011-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1007/s11248-010-9439-9
Volume 20
Issue 3
Start page 557
End page 567
Total pages 11
Place of publication Dordrecht, The Netherlands
Publisher Springer Netherlands
Collection year 2011
Language eng
Subject 06 Biological Sciences
1002 Environmental Biotechnology
Formatted abstract
Growth hormone (GH) gene transfer can markedly increase growth in transgenic fish. In the present study we have developed a transcriptional assay to evaluate GH-signal activation (GHSA) in zebrafish embryos. By analyzing the transcription of c-fos and igf1, and the promoter activity of spi2.1, in zebrafish embryos injected with different constructs, we found that overexpression of either GH or growth hormone receptor (GHR) resulted in GHSA, while a synergetic overexpression of GH and GHR gave greater activation. Conversely, overexpression of a C-terminal truncated dominant-negative GHR (ΔC-GHR) efficiently blocked GHSA epistatic to GH overexpression, demonstrating the requirement for a full GHR homodimer in signaling. In view of the importance of signal-competent GHR dimerization by extracellular GH, we introduced into zebrafish embryos a constitutively activated GHR (CA-GHR) construct, which protein products constitutively dimerize the GHR productively by Jun-zippers to activate downstream signaling in vitro. Importantly, overexpression of CA-GHR led to markedly higher level of GHSA than the synergetic overexpression of GH and GHR. CA-GHR transgenic zebrafish were then studied in a growth trial. The transgenic zebrafish showed higher growth rate than the control fish, which was not achievable by GH transgenesis in these zebrafish. Our study demonstrates GH-independent growth by CA-GHR in vivo which bypasses normal IGF-1 feedback control of GH secretion. This provides a novel means of producing growth enhanced transgenic animals based on molecular protein design.
Keyword GH
GHR
Constitutively active GHR
Protein design
Zebrafish
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online on 29th August 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Sat, 29 Jan 2011, 01:39:38 EST by Susan Allen on behalf of Institute for Molecular Bioscience