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Profound Sex-Specific Effects on Incubation Times for Transmission of Bovine Spongiform Encephalopathy to Mice

Four strains of mice were inoculated intracerebrally with a primary isolate of bovine spongiform encephalopathy (BSE) and the cloned mouse-adapted scrapie strain ME7. Clinical prion disease diagnosis was made at the appearance of three or more neurological symptoms and their persistence for 3 consecutive weeks and confirmed by neuropathological criteria. For BSE, incubation periods were profoundly different between the sexes in all four mouse strains, being longer in the females. In contrast, ME7 scrapie incubation times were similar between the sexes. Our results indicate that sex-specific processes are involved in the course of primary BSE transmission. Research into this phenomenon may provide clues to the prophylaxis of BSE and have possible implications for new variant Creutzfeldt-Jakob disease in humans.