Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice

Cytomegalovirus (CMV) is the most common infectious cause of congenital anomalies of the CNS in humans. We recently reported that the murine cytomegalovirus (MCMV) immediate-early (IE) gene promoter directs astrocyte-specific expression in adult transgenic mice. In the present study, we analyzed the activation of the MCMV IE promoter in developing transgenic mouse brains and compared the activation with that of the Musashi 1 (Msi1) gene, which is expressed in neural progenitor cells, including neural stem cells. During the early phase of neurogenesis, the transgene was expressed predominantly in endothelial cells of the vessels, but not in neuroepithelial cells in which Msi1 was expressed. During later stages of gestation, expression of the transgene was largely restricted to the ventricular zone (VZ) in the CNS, similar to the expression of Msi1. In neurosphere cultures from transgenic embryos in the late phase of neurogenesis, the transgene was expressed in some cells of neurospheres expressing Msi1 and nestin. In neural precursor cells induced to differentiate from stem cells, expression of the transgene was detected in glial progenitor cells, expressing GFAP, nestin, and Msi1, but not in cells expressing MAP2 or MAG. In postnatal development, persistent expression of the transgene was observed in astrocyte lineage cells as was Msi1. These spatiotemporal changes of the MCMV IE promoter activity during development of transgenic mice correlated with susceptible sites in congenital HCMV infection. Moreover, this transgenic mouse model may provide useful model for analysis of the regulation of the switching of neuronal and astrocyte differentiation, and the maintenance of the astrocyte lineage.