An examination of the up-regulation of a circadian gene dbp in the liver tissues of HBsAg positive transgenic mice
LI Xiao-xiao1; REN Jun1; WANG Long2; MA Zhang-mei1; WANG Zhu-gang2; XIE You-hua1.3; Wen Yu-mei1.3
1. Ministry of Education/Ministry of Health Key laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan university, Shanghai 200032, China; 2. Shanghai research center for model organisms, Shanghai 201210, China; 3. Institute of biomedical sciences, Fudan University, Shanghai 200032, China.
摘要: 目的 验证HBsAg阳性转基因小鼠肝脏中昼夜节律表达基因dbp (coding for the D site albumin promoter binding protein)转录水平的变化。 方法 用实时荧光定量聚合酶链式反应方法对比研究雌、雄及个体HBsAg阳性转基因小鼠及对照鼠肝脏dbp转录水平的变化。研究不同时间点HBsAg阳性转基因小鼠及对照鼠肝脏dbp转录水平的变化。 结果 #59 及#10 品系组HBsAg阳性转基因小鼠肝组织中dbp均较对照组动物上调, 但个体间差别较大。初步结果显示雌性正常小鼠dbp转录水平较雄性为高。而在雌性HBsAg阳性转基因小鼠中dbp的上调进一步增强。与此相反，雄性转基因小鼠dbp的上调则较同性对照鼠更弱。转基因小鼠dbp转录，在8：00时及14：00时平均水平均高于对照鼠，然而在20：00时及2：00时则与对照鼠相当。结论 本研究首次报道HBsAg阳性转基因小鼠肝脏中dbp表达的上调，提供了乙型肝炎病毒蛋白表达与昼夜节律基因变化有所联系的证据。至于本研究在转基因鼠中的发现是否在乙型肝炎患者中存在及其意义还有待在患者中作进一步临床验证与研究。
Abstract：Objective To verify the changes of a circadian gene dbp ( coding for the D site albumin promoter binding protein) in liver tissues of HBsAg positive transgenic mice. Methods Real-time fluorescent quantitative PCR was used to compare the transcriptional levels of dbp in male and female HBsAg positive transgenic mice versus their controls. Individual transgenic mouse and mice at different time points were used to study the regulation of dbp. Results In the liver tissues from both #59 and #10 lineages of HBsAg positive transgenic mice, dbp was up-regulated, compared to their control counterparts, but there was marked individual variability. Preliminary results showed that in HBsAg negative female mice, the transcriptional level of dbp was higher than that in male mice. This difference was more marked in HBsAg positive female transgenic mice. At 8:00 and 2:00, dbp was up-regulated in HBsAg positive transgenic mice, compared to the controls. However, at 8:00 and 2:00, the dbp transcriptional levels were similar between HBsAg positive transgenic mice and the controls. Conclusions For the first time it is reported that dbp was up-regulated in HBsAg positive transgenic mice, which provided evidence that HBV protein expression could be associated with changes in a circadian gene. Further studies are needed to confirm whether this up-regulation can also be found in patients, and clarify the implications of this observation.