Neuron-specific activation of murine cytomegalovirus early gene e1 promoter in transgenic mice
Neuron-specific activation of murine cytomegalovirus early gene e1 promoter in transgenic mice
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DOI：
10.1016/s0002-9440(10)63691-7
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发表时间：
2003-08-01
影响因子：
6
通讯作者：
Tsutsui, Y
中科院分区：
文献类型：
--
作者：
Arai, Y;Ishiwata, M;Tsutsui, Y
脑是先天性巨细胞病毒(CMV)感染和免疫功能低下患者的主要靶点。没有确切的证据表明CMV对中枢神经系统(CNS)有特殊的亲和力。在这里，我们产生了带有与报告基因LacZ连接的E1启动子/增强子区的转基因小鼠。令人惊讶的是，在所有转基因小鼠中，转基因的表达完全局限于中枢神经系统。转基因在大脑皮层、海马区、间脑、脑干、小脑和脊髓的神经元亚群中均有表达。中枢神经系统的非神经细胞未见转基因表达。在妊娠晚期，转基因基因首先在中脑的神经元中被激活，然后随着发育的进行，脑内不同部位的阳性神经元数量增加。转基因小鼠脑内感染MCMV后，激活神经元的分布更加广泛，数量增多。这些结果表明，在神经元中存在直接激活巨细胞病毒早期基因启动子的宿主因子(S)。这种神经元特异性激活可能与脑内持续感染有关，并可能与CMV感染引起的神经元功能障碍和神经元丢失有关。
The brain is the main target in congenital cytomegalovirus (CMV) infection and immunocompromised patients. No definite evidence that a CMV has special affinity for the central nervous system (CNS) has been published. Here, we generated transgenic mice with an e1 promoter/enhancer region connected to the reporter gene lacZ. Surprisingly, expression of the transgene was completely restricted to the CNS in all lines of transgenic mice. The transgene was expressed in subpopulation of neurons in the cerebral cortex, hippocampus, diencephalon, brainstem, cerebellum, and spinal cord in all of the fines. Non-neuronal cells in the CNS were negative for transgene expression. Activation of the transgene was first observed in neurons of mesencephalon in late gestation, and then the number of positive neurons increased in various parts of the brain as development proceeded. Upon infection of the transgenic mouse brains with MCMV, the location of the activated neurons became more extensive, and the number of such neurons increased. These results suggest that there are host factor(s) that directly activate the MCMV early gene promoter in neurons. This neuron-specific activation may be associated with persistent infection in the brain and may be responsible for the neuronal dysfunction and neuronal cell loss caused by CMV infection.