Lai Cheng-Wei, Chen Hsiao-Ling, Tsai Tung-Chou, Chu Te-Wei, Yang Shang-Hsun, Chong Kowit-Yu, Chen Chuan-Mu
Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
Department of Bioresources, Da-Yeh University, Changhua 515, Taiwan.
Sci Rep. 2016 Apr 18;6:24023. doi: 10.1038/srep24023.
Sexually dimorphic gene expression is commonly found in the liver, and many of these genes are linked to different incidences of liver diseases between sexes. However, the mechanism of sexually dimorphic expression is still not fully understood. In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty. The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation. Through this de novo sexually dimorphic expression of the transgene, the Akr1A1(eGFP) mouse provides a useful model to study the mechanisms and the dynamic changes of sexually dimorphic gene expression during either development or pathogenesis of the liver.
性二态性基因表达在肝脏中普遍存在，其中许多基因与不同性别间肝脏疾病的发病率差异有关。然而，性二态性表达的机制仍未完全阐明。在本研究中，一种在Akr1A1基因座具有特定转基因整合位点的pCAG-eGFP转基因小鼠品系在肝脏中呈现雄性偏向的EGFP表达，且该表达在青春期被睾酮激活。pCAG-eGFP转基因的整合改变了邻近染色质的表观遗传调控，包括性二态性表达调节因子STAT5b的结合增加，以及DNA甲基化从高甲基化转变为雄性偏向的低甲基化。通过转基因这种从头开始的性二态性表达，Akr1A1(eGFP)小鼠为研究肝脏发育或发病过程中性二态性基因表达的机制和动态变化提供了一个有用的模型。
