Related Experiment Video
Updated: Jun 17, 2026
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
Published on: March 31, 2015
Transgenic expression of walleye dermal sarcoma virus rv-cyclin gene in zebrafish and its suppressive effect on liver
Huiqing Zhan1, Jan M Spitsbergen, Wei Qing
1Department of Biological Sciences, National University of Singapore, Singapore, Singapore 117543.
Abstract:
A retrovirus homologue gene of cellular cyclin D₁, walleye dermal sarcoma virus rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish under the control of liver fatty acid-binding protein (lfabp) promoter. To prevent possible fatality caused by overexpression of the oncogene, the GAL4/upstream activation sequence (GAL4/UAS) system was used to maintain the transgenic lines. Thus, both GAL4-activator [Tg(lfabp:GAL4)] and UAS-effector [Tg(UAS:rvcyclin)] lines were generated, and the rv-cyclin gene was activated in the liver after crossing these two lines. Since no obvious neoplasia phenotypes were observed in the double-transgenic line, cancer susceptibility of the transgenic fish expressing rv-cyclin was tested by carcinogen treatment. Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) were more resistant to the carcinogen than siblings not expressing this gene (rvcyclin-). Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ than in rvcyclin- fish, and the liver tumors in the rvcyclin+ group appeared later and were less malignant. These results suggest that expression of rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy. These findings indicate that transgenic fish models are powerful systems for investigating mechanisms of inhibition and regression of liver tumors.
Insights
The walleye dermal sarcoma virus rv-cyclin gene, when expressed in zebrafish livers, unexpectedly protected against carcinogen-induced liver tumors. Transgenic fish showed reduced tumor incidence and malignancy, suggesting a protective role for rv-cyclin.
Area of Science:
- * Molecular biology
- * Cancer research
- * Zebrafish transgenesis
Background:
- * Cellular cyclin D1 is a key regulator of cell cycle progression.
- * The walleye dermal sarcoma virus rv-cyclin gene is a retroviral homologue of cyclin D1.
- * Oncogene overexpression can lead to fatality, necessitating controlled expression systems.
Purpose of the Study:
- * To investigate the effect of rv-cyclin expression in zebrafish liver on cancer susceptibility.
- * To utilize the GAL4/UAS system for controlled oncogene activation in transgenic fish.
- * To assess the potential protective role of rv-cyclin against carcinogen-induced liver damage.
Main Methods:
- * Generation of transgenic zebrafish lines: Tg(lfabp:GAL4) and Tg(UAS:rvcyclin).
- * Activation of rv-cyclin expression in the liver of double-transgenic fish [Tg(lfabp:GAL4); Tg(UAS:rvcyclin)].
- * Exposure of transgenic fish to a carcinogen to test cancer susceptibility.
Main Results:
- * Transgenic fish expressing rv-cyclin (rvcyclin+) exhibited resistance to carcinogen treatment compared to non-transgenic siblings (rvcyclin-).
- * Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ fish.
- * Liver tumors in the rvcyclin+ group appeared later and were less malignant than in the rvcyclin- group.
Conclusions:
- * Expression of rv-cyclin in zebrafish liver confers protection against carcinogen-induced liver damage.
- * Rv-cyclin expression delays the onset and reduces the malignancy of liver tumors.
- * Transgenic fish models are valuable tools for studying liver tumor inhibition and regression mechanisms.
