Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.
GC Telling, M Scott, KK Hsiao… - Proceedings of the …, 1994 - National Acad Sciences
GC Telling, M Scott, KK Hsiao, D Foster, SL Yang, M Torchia, KC Sidle, J Collinge…
Proceedings of the National Academy of Sciences, 1994•National Acad SciencesTransgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a
segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP
sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids
between residues 96 and 167. All of the Tg (MHu2M) mice developed neurologic disease
approximately 200 days after inoculation with brain homogenates from three patients dying
of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg (MHu2M) mice with CJD prions …
segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP
sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids
between residues 96 and 167. All of the Tg (MHu2M) mice developed neurologic disease
approximately 200 days after inoculation with brain homogenates from three patients dying
of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg (MHu2M) mice with CJD prions …
Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPSc (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPSc. The patterns of MHu2MPrPSc and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.
National Acad Sciences