Activation of murine cytomegalovirus immediate-early promoter in mouse brain after transplantation of the neural stem cells.
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.
Li
Ren-Yong
RY
Second Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu, Japan.
Kosugi
Isao
I
Tsutsui
Yoshihiro
Y
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000821:virology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000151:congenital / Q000235:genetics; D004622:Embryo, Mammalian; D005697:Galactosides / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007211:Indoles / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000235:genetics* / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D009474:Neurons / Q000637:transplantation / Q000821:virology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013234:Stem Cells / Q000166:cytology / Q000821:virology*; D013997:Time Factors
D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D004676:Myelin Basic Protein; D010751:Phosphopyruvate Hydratase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside