Burk R D, DeLoia J A, elAwady M K, Gearhart J D
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461.
J Virol. 1988 Feb;62(2):649-54. doi: 10.1128/JVI.62.2.649-654.1988.
Two transgenic mice were produced by microinjection of the entire hepatitis B virus (HBV) genome as a 3.2-kilobase EcoRI DNA fragment into one-cell embryos. Each animal contained a single, unique locus of HBV sequence. One founder animal, G7, contained a partially deleted HBV genome lacking both putative HBV surface antigen (HBsAg) promoters. The other animal, G26, contained greater-than-genome-length HBV sequences organized as a partial head-to-tail dimer. Both transgenic animals transmitted the HBV sequences in a Mendelian fashion, and all subsequent transgenic animals had detectable HBsAg in the serum. Expression of HBV sequences in tissues from G7- and G26-derived mice showed preferential expression of the 2.1-kilobase HBsAg RNA transcript in liver and kidney tissues by Northern (RNA) blot analysis. These data are consistent with the notion that HBV DNA contains cis-acting regulatory sequences which are responsible for the predominant expression of HBsAg transcripts in the liver and kidney of transgenic mice.
通过将整个乙型肝炎病毒(HBV)基因组作为一个3.2千碱基的EcoRI DNA片段显微注射到单细胞胚胎中,培育出了两只转基因小鼠。每只动物都含有一个单一、独特的HBV序列位点。一只奠基动物G7含有一个部分缺失的HBV基因组,该基因组缺少两个假定的HBV表面抗原(HBsAg)启动子。另一只动物G26含有大于基因组长度的HBV序列,这些序列组织成一个部分头对头的二聚体。两只转基因动物都以孟德尔方式传递HBV序列,并且所有后续的转基因动物血清中都可检测到HBsAg。通过Northern(RNA)印迹分析,来自G7和G26衍生小鼠的组织中HBV序列的表达显示,2.1千碱基的HBsAg RNA转录本在肝脏和肾脏组织中优先表达。这些数据与以下观点一致,即HBV DNA包含顺式作用调节序列,这些序列负责转基因小鼠肝脏和肾脏中HBsAg转录本的主要表达。