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两株乙型肝炎病毒转基因小鼠中乙型肝炎表面抗原表达的发育调控

Developmental regulation of hepatitis B surface antigen expression in two lines of hepatitis B virus transgenic mice.

作者信息

DeLoia J A, Burk R D, Gearhart J D

机构信息

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

出版信息

J Virol. 1989 Sep;63(9):4069-73. doi: 10.1128/JVI.63.9.4069-4073.1989.

DOI:10.1128/JVI.63.9.4069-4073.1989
PMID:2760988
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC251009/
Abstract

Two lines of hepatitis B virus (HBV) transgenic mice, designated G7 and G26, show preferential expression of the 2.1-kilobase hepatitis B surface antigen (HBsAg) RNA transcript in liver and kidney tissues (R. D. Burk, J. A. DeLoia, M. K. ElAwady, and J. D. Gearhart, J. Virol 62:649-654, 1988). This transcript was first identified in transgenic mice at gestational day 14 and was detected at similar or increased levels through birth and early development. However, in contrast to 2.1-kilobase HBsAg mRNA levels, HBsAg protein levels in serum decreased shortly after birth. Thereafter, serum HBsAg increased 100-fold to adult levels, with a corresponding 5- to 10-fold increase in HBsAg mRNA levels. In addition, adult males have higher levels of HBsAg in serum than females. HBsAg in serum in males was reduced approximately 50% by surgical castration and was restored to near-normal levels by testosterone supplementation. Since both transgenic lines show similar patterns of gene expression, we suggest that HBsAg gene expression is determined by viral regulatory elements in response to host factors. Whether tissue specificity, developmental regulation, and sexual dimorphism of expression of the exogenous HBV sequences were determined by single or multiple HBV regulatory elements remains to be determined.

摘要

两株乙型肝炎病毒(HBV)转基因小鼠,分别命名为G7和G26,在肝脏和肾脏组织中显示出2.1千碱基乙型肝炎表面抗原(HBsAg)RNA转录本的优先表达(R.D.伯克、J.A.德洛亚、M.K.埃拉瓦迪和J.D.吉尔哈特,《病毒学杂志》62:649 - 654,1988年)。这种转录本在妊娠第14天首次在转基因小鼠中被鉴定出来,并且在出生及早期发育过程中以相似或增加的水平被检测到。然而,与2.1千碱基HBsAg mRNA水平不同,血清中的HBsAg蛋白水平在出生后不久就下降了。此后,血清HBsAg增加到成年水平的100倍,同时HBsAg mRNA水平相应增加5至10倍。此外,成年雄性血清中的HBsAg水平高于雌性。雄性血清中的HBsAg通过手术去势降低了约50%,并通过补充睾酮恢复到接近正常水平。由于这两个转基因品系显示出相似的基因表达模式,我们认为HBsAg基因表达是由病毒调控元件响应宿主因子而决定的。外源性HBV序列表达的组织特异性、发育调控和性别差异是由单个还是多个HBV调控元件决定仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ce/251009/dde1625a8634/jvirol00076-0527-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ce/251009/dde1625a8634/jvirol00076-0527-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ce/251009/dde1625a8634/jvirol00076-0527-a.jpg

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Proc Natl Acad Sci U S A. 1987 Mar;84(5):1187-91. doi: 10.1073/pnas.84.5.1187.