Activation of murine cytomegalovirus immediate-early promoter in mouse brain after transplantation of the neural stem cells
Activation of murine cytomegalovirus immediate-early promoter in mouse brain after transplantation of the neural stem cells
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DOI：
10.1007/s00401-004-0828-0
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发表时间：
2004-03
影响因子：
12.7
通讯作者：
Ren‐Yong Li;I. Kosugi;Y. Tsutsui
中科院分区：
文献类型：
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作者：
Ren‐Yong Li;I. Kosugi;Y. Tsutsui
巨细胞病毒（CMV）是免疫功能低下患者先天性感染和致死性疾病的最重要的感染原因。我们以前已经描述了一个转基因小鼠模型的小鼠CMV（MCMV）立即早期（IE）基因启动子融合lacZ报告基因（MCMV-IE-pro 1）的启动子活性在大脑发育过程中的时空变化的分析。由于IE基因的表达在潜伏期和再激活中起着关键作用，我们将表达转基因的神经干细胞（NSCs）移植到新生小鼠脑中，用溴脱氧尿苷（BrdU）标记后。MCMV IE pro 1在移植后即刻在室管膜下区（SVZ）被激活，随着发育进程MCMV IE pro 1激活的细胞逐渐减少。移植后4周，皮质内可见MCMV IE pro 1激活的胶质酸性蛋白阳性细胞，但BrdU染色阴性; SVZ内仍有BrdU阳性细胞，但MCMV IE pro 1激活的胶质酸性蛋白阳性细胞不存在。BALB/c小鼠同种异体移植后，MCMV IE启动子活性在皮层易于检测。这些结果表明，SVZ是MCMV IE启动子在新生小鼠移植后早期激活的最敏感位点，大脑皮层也是移植后后期激活的敏感位点。避免使用CMV潜伏感染的NSC作为供体细胞可能是重要的。
Cytomegalovirus (CMV) is the most significant infectious cause of congenital infection and fatal diseases in immunocompromised patients. We have previously described a transgenic mouse model of the murine CMV (MCMV) immediate-early (IE) gene promoter fused with the lacZ reporter gene (MCMV-IE-pro1) for the analysis of spatiotemporal changes of the promoter activity during brain development. Since expression of the IE genes play a pivotal role in latency and reactivation, we transplanted the transgene-expressing neural stem cells (NSCs) into neonatal mouse brains after labeling with bromodeoxyuridine (BrdU). The activation of MCMV-IE pro1 was detected in the subventricular zone (SVZ) soon after transplantation, and the number of MCMV IE pro1-activated cells was decreased as the development proceeded. Cells that were MCMV IE pro1-activated and glial fibrillary acidic protein positive, but not stained with BrdU, were found in the cortex 4 weeks after transplantation, while BrdU-positive but not MCMV IE pro1-activated cells still existed in the SVZ. MCMV IE promoter activity tended to be easily detected in the cortex after allogenic transplantation in BALB/c mouse. These results suggest that the SVZ is the most susceptible site for activation of the MCMV IE promoter in neonatal mice in the early period after transplantation and that the cerebral cortex is also susceptible to the activation in the late period after transplantation. It may be important to avoid the use of NSCs latently infected with CMV as donor cells.