Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes

M Scott, D Groth, D Foster, M Torchia, SL Yang… - Cell, 1993 - cell.com
M Scott, D Groth, D Foster, M Torchia, SL Yang, SJ DeArmond, SB Prusiner
Cell, 1993cell.com
Transgenic mice expressing chimeric prion protein (PrP) genes derived from Syrian hamster
(SHa) and mouse (MO) PrP genes were constructed. One SHa/MoPrP gene, designated
MHSM PrP, contains five amino acid substitutions encoded by SHaPrP, while another
construct, designated MHMP PrP, has two substitutions. Transgenic (Tg)(MHPM PrP) mice
were susceptible to both Syrian hamster and mouse prions, whereas three lines expressing
MHM2 PrP were resistant to Syrian hamster prions. The brains of Tg (MH2M PrP) mice dying …
Summary
Transgenic mice expressing chimeric prion protein (PrP) genes derived from Syrian hamster (SHa) and mouse (MO) PrP genes were constructed. One SHa/MoPrP gene, designated MHSM PrP, contains five amino acid substitutions encoded by SHaPrP, while another construct, designated MHMP PrP, has two substitutions. Transgenic (Tg)(MHPM PrP) mice were susceptible to both Syrian hamster and mouse prions, whereas three lines expressing MHM2 PrP were resistant to Syrian hamster prions. The brains of Tg (MH2M PrP) mice dying of scrapie contained chimeric PrPSC and prions with an artificial host range favoring propagation in mice that express the corresponding chimeric PrP and were also transmissible, at reduced efficiency, to nontransgenic mice and hamsters. Our findings provide genetic evidence for homophilic interactions between PrPr in the inoculum and PrPC synthesized by the host.
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