Murine cytomegalovirus immediate-early promoter directs astrocyte-specificexpression in transgenic mice

Murine cytomegalovirus (MCMV), which causes acute, latent, and persistent i nfection of the natural host, is used as an animal model of human cytomegal ovirus (HCMV) Infection. Transcription of MCMV immediate-early (IE) genes i s required for expression of the early and late genes and is dependent on h ost cell transcription factors. Cell-type-specific expression activity of t he MCMV IE promoter was analyzed in transgenic mice generated with the majo r IE (MIE) enhancer/promoter involving nucleotides -1343 to -6 (1338 bp) co nnected to the reporter gene lacZ. Distinct expression was observed in the brain, kidneys, stomach, and skeletal muscles. Weak expression was observed in a portion of the parenchymal cells of the salivary glands and pancreas, and expression was hardly detected in the lungs, Intestine, or immune and hematopoietic organs such as the thymus, spleen, lymph nodes, and bone marr ow. The spectrum of organs positive for expression was narrower than that o f the HCMV MIE promoter-lacZ transgenic mice reported previously and showed a greater degree of cell-type specificity. Interestingly, astrocyte-specif ic expression of the transgene was observed in the brain and primary glial cultures from the transgenic mice by combination of beta-galactosidase (bet a-Gal) expression and. immunostaining for cell markers. However, the transg ene was not expressed in neurons, oligodendroglia, microglia, or endothelia l cells. Furthermore, the beta-Gal expression in glial cultures was stimula ted significantly by MCMV infection or by addition of calcium ionophore. Th ese observations indicated that expression activity of the MCMV IE promoter Is strictly cell-type specific, especially astrocyte-specific in the brain . This specific pattern of activity is similar to that of natural HCMV Infe ction in humans.