SERIAL TRANSMISSION IN RODENTS OF NEURODEGENERATION FROM TRANSGENIC MICE EXPRESSING MUTANT PRION PROTEIN

Two lines of transgenic (Tg) mice expressing high (H) levels of the mu tant P101L prion protein (PrP) developed a neurologic illness and cent ral nervous system pathology indistinguishable from experimental murin e scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogena tes from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD -1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximate to 10% of hams ters and approximate to 40% of the Tg196 mice manifested neurologic si gns between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated wit h brain extracts, producing incubation times of approximate to 400 and approximate to 75 days, respectively. Although the Tg(MoPrP-P101L)H m ice appear to accumulate only low levels of infectious prions in their brains, the serial transmission of disease to inoculated recipients a rgues that prion formation occurs de novo in the brains of these unino culated animals. These Tg mouse studies, taken together with similar f indings in humans dying of inherited prion diseases, provide additiona l evidence that prions lack a foreign nucleic acid.