title: Biological and biochemical characterization of mice expressing prion protein devoid of the octapeptide repeat region after infection with prions.
abstract: Accumulating lines of evidence indicate that the N-terminal domain of prion protein (PrP) is involved in prion susceptibility in mice. In this study, to investigate the role of the octapeptide repeat (OR) region alone in the N-terminal domain for the susceptibility and pathogenesis of prion disease, we intracerebrally inoculated RML scrapie prions into tg(PrPΔOR)/Prnp(0/0) mice, which express mouse PrP missing only the OR region on the PrP-null background. Incubation times of these mice were not extended. Protease-resistant PrPΔOR, or PrP(Sc)ΔOR, was easily detectable but lower in the brains of these mice, compared to that in control wild-type mice. Consistently, prion titers were slightly lower and astrogliosis was milder in their brains. However, in their spinal cords, PrP(Sc)ΔOR and prion titers were abundant and astrogliosis was as strong as in control wild-type mice. These results indicate that the role of the OR region in prion susceptibility and pathogenesis of the disease is limited. We also found that the PrP(Sc)ΔOR, including the pre-OR residues 23-50, was unusually protease-resistant, indicating that deletion of the OR region could cause structural changes to the pre-OR region upon prion infection, leading to formation of a protease-resistant structure for the pre-OR region.
authors.affiliation: Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), The University of Tokushima, Tokushima, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hironori
authors.initials: H
authors.lastname: Miyata
authors.forename: Keiji
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Ootsuyama
authors.forename: Sachiko
authors.initials: S
authors.lastname: Inubushi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mori
authors.forename: Naomi
authors.initials: N
authors.lastname: Muramatsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Katamine
authors.forename: Suehiro
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004198:Disease Susceptibility; D019286:Endopeptidase K / Q000378:metabolism; D005552:Forelimb; D005786:Gene Expression Regulation; D008239:Lysine; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000737:chemistry; D010291:Paresis / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D012608:Scrapie / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D009842:Oligopeptides; D011328:Prions; D019286:Endopeptidase K; D008239:Lysine