NEURON-SPECIFIC EXPRESSION OF A HAMSTER PRION PROTEIN MINIGENE IN TRANSGENIC MICE INDUCES SUSCEPTIBILITY TO HAMSTER SCRAPIE AGENT

To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic m ice using al kb hamster cDNA clone containing the 0.76 kb HPrP open re ading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was detected only in brain tissue, with highest levels found in neurons of the cerebellum, hippocampus, thala mus, and cerebral cortex. These transgenic mice were susceptible to in fection by the 263K strain of hamster scrapie with an average incubati on period of 93 days, compared to 72 days in normal hamsters. In contr ast, nontransgenic mice were not susceptible to this agent. These resu lts indicate that neuron-specific expression of the 1 kb HPrP minigene including the HPrP open-reading frame is sufficient to mediate suscep tibility to hamster scrapie, and that HPrP expression in nonneuronal b rain cells is not necessary to overcome the TSE species barrier.