title: Tracing conformational transition of abnormal prion proteins during interspecies transmission by using novel antibodies.
abstract: Conformational differences in abnormal prion proteins (PrP(Sc)) have been postulated to produce different prion phenotypes. During the interspecies transmission of prions, the conformation of PrP(Sc) may change with passage; however, little is known about the mechanism of PrP(Sc) transition. In this study, novel PrP(Sc)-specific monoclonal antibodies (mAbs) were developed that could detect the PrP(Sc) of mouse but not that of sheep. By using these mAbs, we attempted to examine PrP(Sc) accumulated in mice inoculated with sheep scrapie serially up to five passages. The presence of PrP(Sc) in the mice was confirmed at all passages; however, mAb-bound PrP(Sc) conformer was detected only from the third passage onward. The generated mAb enabled tracing of a particular conformer during adaptation in sheep-to-mice transmission of prion, suggesting that the conformational transition of PrP(Sc) was caused by propagation of this conformer. Such mAbs capable of discriminating conformational differences may allow us to address questions concerning PrP(Sc) conformation and strain diversity.
authors.affiliation: Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ushiki-Kaku
authors.forename: Ryo
authors.initials: R
authors.lastname: Endo
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Iwamaru
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Morikazu
authors.initials: M
authors.lastname: Imamura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Masujin
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Shunji
authors.initials: S
authors.lastname: Hattori
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Irie
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D006224:Cricetinae; D008647:Mesocricetus; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010641:Phenotype; D018620:PrPSc Proteins / Q000737:chemistry* / Q000276:immunology* / Q000472:pathogenicity; D017096:Prion Diseases / Q000378:metabolism* / Q000635:transmission*; D011328:Prions / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D012608:Scrapie / Q000378:metabolism / Q000635:transmission; D012756:Sheep; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D018620:PrPSc Proteins; D011328:Prions