Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

The expression of the cellular form of the prion protein (PrPc) gene is req uired for prion replication and neuroinvasion in transmissible spongiform e ncephalopathies. The identification of the cell types expressing PrPc is ne cessary to understanding how the agent replicates and spreads from peripher al sites to the central nervous system. To determine the nature of the cell types expressing PrPc, a green fluorescent protein reporter gene was expre ssed in transgenic mice under the control of 6.9 kb of the bovine PrP gene regulatory sequences. It was shown that the bovine PrP gene is expressed as two populations of mRNA differing by alternative splicing of one 115-bp 5' untranslated exon in 17 different bovine tissues. The analysis of transgen ic mice showed reporter gene expression in some cells that have been identi fied as expressing PrP, such as cerebellar Purkinje cells, lymphocytes, and keratinocytes. In addition, expression of green fluorescent protein was ob served in the plexus of the enteric nervous system and in a restricted subs et of cells not yet clearly identified as expressing PrP: the epithelial ce lls of the thymic medullary and the endothelial cells of both the mucosal c apillaries of the intestine and the renal capillaries. These data provide v aluable information on the distribution of PrPc at the cellular level and a rgue for roles of the epithelial and endothelial cells in the spread of inf ection from the periphery to the brain. Moreover, the transgenic mice descr ibed in this paper provide a model that will allow for the study of the tra nscriptional activity of the PrP gene promoter in response to scrapie infec tion.