論文

国際誌
2020年10月1日

Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91-106.

International journal of molecular sciences
  • Keiji Uchiyama
  • ,
  • Hironori Miyata
  • ,
  • Yoshitaka Yamaguchi
  • ,
  • Morikazu Imamura
  • ,
  • Mariya Okazaki
  • ,
  • Agriani Dini Pasiana
  • ,
  • Junji Chida
  • ,
  • Hideyuki Hara
  • ,
  • Ryuichiro Atarashi
  • ,
  • Hitomi Watanabe
  • ,
  • Gen Kondoh
  • ,
  • Suehiro Sakaguchi

21
19
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms21197260

Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91-106 were generated in the absence of endogenous PrPC, designated Tg(PrP∆91-106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrP∆91-106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPSc∆91-106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPSc∆91-106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrPSc∆91-104 after incubation with BSE-PrPSc-prions but not with RML- and 22L-PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91-104 into PrPSc∆91-104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91-106 or 91-104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.

リンク情報
DOI
https://doi.org/10.3390/ijms21197260
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33019549
ID情報
  • DOI : 10.3390/ijms21197260
  • PubMed ID : 33019549

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