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biological and biochemical characterization of mice expressing prion protein devoid of the octapeptide repeat region after infection with prions生物和生化特性的老鼠朊蛋白表达缺乏感染朊病毒后八肽重复区域.pdf

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Biological and Biochemical Characterization of Mice Expressing Prion Protein Devoid of the Octapeptide Repeat Region after Infection with Prions 1,2 3 1 4 1 Yoshitaka Yamaguchi , Hironori Miyata , Keiji Uchiyama , Akira Ootsuyama , Sachiko Inubushi , 1 1 2 1,2 Tsuyoshi Mori , Naomi Muramatsu , Shigeru Katamine , Suehiro Sakaguchi * 1 Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), The University of Tokushima, Tokushima, Japan, 2 Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, 3 Animal Research Center, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 4 Department of Radiation Biology and Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan 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(PrPDOR)/Prnp0/ 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 PrPDOR, or PrPScDOR, 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 m
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