Susceptibility of Transgenic mice expressing chimeric sheep, bovine and human PrP genes to sheep scrapie

Altangerel Gombojav, Ikuko Shimauchi, Motohiro Horiuchi, Naotaka Ishiguro, Morikazu Shinagawa, Tetsuyuki Kitamoto, Ichiro Miyoshi, Shirou Mohri, Masuhiro Takata

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The use of Transgenic (Tg) mice expressing chimeric sheep/mouse (Sh/Mo) prion protein (PrP) and chimeric bovine/mouse (Bo/Mo) PrP genes was evaluated as a sheep scrapie model. We also investigated the potential for the transmission of sheep scrapie to a human/mouse (Hu/Mo) PrP Tg mouse line. The Sh/Mo PrP and Bo/Mo PrP Tg Prnp+/+ or Prnp0/0 mouse lines were inoculated intracerebrally with brain homogenates from three sheep with natural scrapie (KU, Y5 or S2). Incubation periods were slightly shorter in Sh/Mo PrP Tg Prnp+/+, than in non-Tg mice inoculated with KU brain homogenate. In contrast, the incubation period was significantly prolonged (p<0.05) in Bo/Mo PrP Tg Prnp+/+ mice inoculated with KU brain homogenate. The incubation period was significantly longer in all Tg Prnp+/+ and Prnp0/0, than in non-Tg mice (p<0.01) inoculated withY5 brain homogenate. None of the Tg Prnp0/0 mice inoculated with S2 brain homogenate developed clinical signs and PrPSc was undetectable in their brains. These results suggested that expression of the Sh/Mo PrP or Bo/Mo PrP transgenes does not confer susceptibility to sheep prions upon mice, and thus none of the Tg mouse lines could be a suitable model of sheep scrapie. Hu/Mo PrP Tg Prnp0/0 mice inoculated with natural and experimental scrapie or mouse prions did not develop clinical signs of scrapie and PrP Sc was undetectable. These results suggested that neither sheep nor mouse strains of scrapie are highly transmissible to humans.

Original languageEnglish
Pages (from-to)341-347
Number of pages7
JournalJournal of Veterinary Medical Science
Volume65
Issue number3
DOIs
Publication statusPublished - 2003 Mar

Keywords

  • PrP transgene
  • Prion
  • Scrapie susceptibility
  • Transgenic mouse

ASJC Scopus subject areas

  • veterinary(all)

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