Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct
文献类型：期刊论文
| 作者 | Ahmed, A. S. Ishtiaq1,4; Xiong, Feng1,4; Pang, Shao-Chen1,4; He, Mu-Dan1,4; Waters, Michael J.2,3; Zhu, Zuo-Yan1; Sun, Yong-Hua1 |
| 刊名 | TRANSGENIC RESEARCH
 |
| 出版日期 | 2011-06-01 |
| 卷号 | 20期号:3页码:557-567 |
| 关键词 | GH GHR Constitutively active GHR Protein design Zebrafish |
| ISSN号 | 0962-8819 |
| 通讯作者 | Sun, YH, Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China ; sunyonghua@gmail.com |
| 中文摘要 | 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 (Delta C-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. |
| 英文摘要 | 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 (Delta C-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. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology |
| 类目[WOS] | Biochemical Research Methods ; Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology |
| 关键词[WOS] | TRANSGENIC FISH ; HORMONE RECEPTORS ; GENE-EXPRESSION ; COMMON CARP ; EMBRYOS ; TRANSCRIPTION ; TROUT ; TEMPERATURES ; TRANSDUCER ; MECHANISMS |
| 收录类别 | SCI |
| 资助信息 | China 973 Project [2010CB126306]; National Natural Science Foundation of China [30972248, 30771100]; China 863 project [2007AA10Z186]; Youth Sunshine Project of Wuhan City ; Institute of Hydrobiology, CAS |
| 语种 | 英语 |
| WOS记录号 | WOS:000290446200011 |
| 公开日期 | 2011-06-30 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/15620]  |
| 专题 | 水生生物研究所_鱼类生物学及渔业生物技术研究中心_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China 2.Univ Queensland, Dept Physiol & Pharmacol, St Lucia, Qld 4072, Australia 3.Univ Queensland, Ctr Mol & Cellular Biol, St Lucia, Qld 4072, Australia 4.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ahmed, A. S. Ishtiaq,Xiong, Feng,Pang, Shao-Chen,et al. Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct[J]. TRANSGENIC RESEARCH,2011,20(3):557-567. |
| APA | Ahmed, A. S. Ishtiaq.,Xiong, Feng.,Pang, Shao-Chen.,He, Mu-Dan.,Waters, Michael J..,...&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. |
| MLA | Ahmed, A. S. Ishtiaq,et al."Activation of GH signaling and GH-independent stimulation of growth in zebrafish by introduction of a constitutively activated GHR construct".TRANSGENIC RESEARCH 20.3(2011):557-567. |
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来源：水生生物研究所
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