Tohoku university school of medicine

Objective- The Division of CJD Science and Technology aims at developing methods to prevent prion diseases. There are two directions of our main research.

① Establishment of animal models for human prion diseases

Bioassays for human prion have been performed conventionally using wild-type mice and required long incubation period (more than 600 days). We established knock-in mice expressing human prion protein and shortened the incubation period to less than 150 days.

Furthermore, we developed a new assay for human prion using the follicular dendritic cells of knock-in mice and shortened the observation period to 14 days. The transmission study using humanized knock-in mice revealed novel properties of prion, e.g., traceback and heterozygous inhibition.

② Elucidation of the conversion mechanism of prion protein

We are studying which domains of prion protein are essential for the conversion.

1)Human PrP^Sc 219K is converted to PrPSc but shows heterozygous inhibition in vCJD infection J. Biol. Chem. In Press 2008 2)Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain J. Biol. Chem. 282(41): 30022-30028 2007

3)vCJD prion acquires altered virulence through trans-species infection Biochem. Biophys. Res. Commun. 342(1): 293-299 2006

4)Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions Biochem. Biophys. Res. Commun. 294(2): 280-286 2002

5)Thr but Asn of the N-glycosylation sites of PrP is indispensable for its misfolding Biochem. Biophys. Res. Commun. 369(4): 1195-1198 2008

Prion, Creutzfeldt-Jakob disease, Bovine spongiform encephalopathy, Knock-in mouse, Transmission, Amino acid substitution, Polymorphism, PMCA, Neuropathology, Brain