Regulatory Function of Proto-oncogene MDM2 on the Liver Growth and Morphogenesis in Zebrafish (Danio rerio)
Date Issued
2005
Date
2005
Author(s)
Huang, Shin-Jie
DOI
zh-TW
Abstract
Mouse double minute-2 (mdm2) gene has been shown to be overexpressed in many cancers that presumably lead to the inactivation of tumor suppressor protein p53. In
addition,MDM2 also has p53-independent functions and plays significant roles in cell cycle control, differentiation, cell fate determination, DNA repair, basal transcription,
and other processes. Moreover, MDM2 overexpression has been demonstrated to have growth arrest function in different animal model such as mice, drosophila and zebrafish . In the present study we made an attempt to study the inhibitory effect of MDM2 overexpression in the growth of liver. We had already developed a liver-GFP
zebrafish transgenic line, a unique tool that can be used to examine liver morphogenesis. Here we used, liver fatty acid binding protein (L-FABP) promoter to drive the mdm2 expression in a liver-specific manner. “Various concentractions of DNA were microinjected and tested, 200 nanogram/microliter was chosen for the next experiments”. The results revealed that overexpression of MDM-2 cause the inhibition of liver growth and ultimately resuled in hypoplasia of the liver. Histopathological studies using HE staining in 4 dpf zebrafish showed the intact
hepatocytes in the wild type liver tissue when compared to the MDM2 transient expressed zebrafish. Using semi-quantitative PCR, we found that some genes involved in the regulation of the cell cycle such as RB-1, β-catenin,Sp1 and TGF-β and liver growth genes such as Hnf-1α, Hnf4α and Ntl have been down-regulated,suggesting the possible role of MDM2 in cell cycle and liver development. The hypoplasic liver may have resulted from cell cycle disorder.Hence, zebrafish liver provides a unique experimental model to explore the molecular interactions of MDM2 in liver morphogenesis.
Subjects
肝臟
斑馬魚
MDM2
LIVER
SDGs
Type
other
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