The expression of viral and cellular genes in papillomas of the choroid plexus induced in transgenic mice.

A line of transgenic mice that carry the SV40 gene for the large Tumor antigen express this protein during the first two weeks of life in brain tissue. By 30-40 days after birth, independently derived multiple foci of abnormal cells appear throughout the choroid plexus. After 90 days, higher levels of T antigen and rapid tumor growth are detected and all these animals die in a narrow time span, between 100-120 days. In situ hybridization with tissue sections and Northern blot analysis have been employed to follow the steady state levels of SV40 RNA and the p53 oncogene RNA levels in normal and tumor tissues. The level of SV40 RNA is quite variable between tumor cells in a section. This heterogeneity of T antigen mRNA levels could permit the selection of cells (from the multiple foci) expressing higher levels of T antigen and growing more rapidly. The increased levels of p53 RNA observed in tumor cells could then result from the active growth state of these cells or a more direct transcriptional activation. Two cellular genes, transthyretin and the 5-HT1C serotonin receptor, both of which are preferentially expressed in normal choroid plexus cells, were also examined for RNA production in these tumors of the choroid plexus. Both of these genes produced high levels of RNA in tumor tissue indicating the retention of well differentiated gene expression in these tumor tissues. This reflects, at the level of gene expression, the well differentiated morphology of these papillomas of the choroid plexus. Interestingly, as cell lines have been derived from these tumors, both the choroid plexus specific RNA species (for 5-HT1C receptor) and characteristic morphology were lost and an increase in T antigen levels was observed.