title: Susceptibility of transgenic mice expressing chimeric sheep, bovine and human PrP genes to sheep scrapie.
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 Prnp(0/0) 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 Prnp(0/0), than in non-Tg mice (p<0.01) inoculated withY5 brain homogenate. None of the Tg Prnp(0/0) mice inoculated with S2 brain homogenate developed clinical signs and PrP(Sc) 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 Prnp(0/0) 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.
authors.affiliation: Laboratory of Veterinary Public Health, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.
authors.forename: Altangerel
authors.initials: A
authors.lastname: Gombojav
authors.forename: Ikuko
authors.initials: I
authors.lastname: Shimauchi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Morikazu
authors.initials: M
authors.lastname: Shinagawa
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Shirou
authors.initials: S
authors.lastname: Mohri
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takata
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000032:analysis / Q000235:genetics; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012608:Scrapie / Q000235:genetics* / Q000635:transmission*; D012757:Sheep Diseases / Q000235:genetics* / Q000635:transmission*; D034561:Sheep, Domestic / Q000235:genetics*; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
chemical_list: D018620:PrPSc Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins