National Institute of Animal Health (NIAH)

Topics in Animal Health Research 2010

05. Tracing conformational transition of abnormal prion proteins during interspecies transmission by using novel antibodies

Japanese

  Conformational differences in abnormal prion proteins (PrPSc) have been postulated to produce different prion phenotypes. During the interspecies transmission of prions, the conformation of PrPSc may change with passage; however, little is known about the mechanism of PrPSc transition. In this study, novel PrPSc-specific monoclonal antibodies (mAbs) were developed that could detect the PrPSc of mouse but not that of sheep. By using these mAbs, we attmpted to examine PrPSc that accumulated in mice inoculated with sheep scrapie serially up to 5 passages. The presence of PrPSc in the mice was confirmed at all passages; however, the mAb-bound PrPSc 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 the prion, suggesting that the conformational transition of PrPSc was caused by propagation of this conformer. Such mAbs capable of discriminating conformational differences may allow us to address questions concerning PrPSc conformation and strain diversity.
(Research Center for Prion Diseases)

References:

Ushiki-Kaku Y. et al. (2010) J. Biol. Chem. 285 (16): 11931-11936

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