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在转基因小鼠中,人转铁蛋白的表达可由兔转铁蛋白调控元件有效调控。

Expression of human transferrin can be regulated effectively by rabbit transferrin regulatory elements in transgenic mice.

作者信息

Yan Jingbin, Gong Xiuli, Pan Shubiao, Guo Xinbing, Ren Zhaorui, Zeng Yitao

机构信息

Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiaotong University, 24/1400 West Beijing Road, Shanghai, 200040, People's Republic of China.

出版信息

Biotechnol Lett. 2014 Jun;36(6):1209-16. doi: 10.1007/s10529-014-1484-7. Epub 2014 Feb 22.

Abstract

Human transferrin (hTF) belongs to the iron-binding glycoprotein family. It plays an important role in iron transport throughout the body. Transgenic mice are a good model to study how to produce functional hTF on a large-scale. We have improved the expression of hTF and investigated its regulatory mechanism in transgenic mice. Three expression constructs were prepared in which hTF expression was controlled by different regulatory cassettes of rabbit transferrin (rTF). hTF was secreted into serum of transgenic mice when its expression was controlled by the rTF promoter and enhancer, whereas the rTF enhancer in tandem with the rTF promoter repressed hTF secretion into milk. A significant inverse relationship between methylation of the rTF promoter and hTF expression was observed in liver, heart, mammary gland, and muscle of transgenic mice. The highest concentration of hTF was 700 μg/ml in milk.

摘要

人转铁蛋白(hTF)属于铁结合糖蛋白家族。它在全身铁运输中发挥着重要作用。转基因小鼠是研究如何大规模生产功能性hTF的良好模型。我们提高了hTF在转基因小鼠中的表达,并研究了其调控机制。制备了三种表达构建体,其中hTF的表达由兔转铁蛋白(rTF)的不同调控盒控制。当hTF的表达由rTF启动子和增强子控制时,它分泌到转基因小鼠的血清中,而与rTF启动子串联的rTF增强子则抑制hTF分泌到乳汁中。在转基因小鼠的肝脏、心脏、乳腺和肌肉中,观察到rTF启动子甲基化与hTF表达之间存在显著的负相关关系。乳汁中hTF的最高浓度为700μg/ml。

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