In vivo glioma model enabling regulated gene expression

Experimental investigation of glioma biology and therapy requires a represe ntative model and a convenient technique for regulating gene expression. We have established an in vivo model in which genetically modified rat C6 gli oma cells (C6TL cells) are transplanted into nude mice brain, followed by s pecific transcriptional control of a transgene. Histologically, the tumors exhibit an astrocytic phenotype and closely resemble human malignant glioma s including diffuse brain invasion. Due to a stably integrated lacZ gene, i ndividual tumor cells can be unequivocally identified in tissue sections by histochemistry for beta-galactosidase. Since C6TL cells carry the ter tran sactivator (tTA) gene, any additional gene under control of a tetracycline/ tTA-responsive promoter can be transcriptionally regulated by the concentra tion of tetracycline. C6TL cells stably transfected with a tetracycline/tTA -responsive luciferase reporter gene showed 23-fold regulation of luciferas e activity in vitro. After intracerebral transplantation a regulation of 4. 5- to 8.3-fold was obtained, dependent on the concentration and the type of tetracycline in the drinking water. This model should be useful for studyi ng the functional role of candidate genes in tumor biology as well as for e xperimental gene therapy studies.