| Research Abstract |
To make a sensitive bioassay system for human prions, we established the transgenic mice with human/mouse chimeric prion protein. We have 3 transgenic lines with codon 129 Met prion protein, and 2 lines with codon 129 Val. Transgenic lines showed various expression level of recombinant prion protein from 0.6 times to 18 times, comparing with the expression of wild-type mouse. The low expression lines (0.6 or 1.2 times) with ablated background showed the shortest incubation period (approximately 150 days) after the intracerebral inoculation of the brain tissues from a patient with sporadic Creutzfeldt-Jakob disease (CJD) (wild type : codon 129 Met/Met, codon 219 Glu/Glu), and the medium expression lines (2 or 4 times) showed the long incubation period. The high expression lines (9 or 18 times) were seen to be inadequate for the transmission experiment because of showing the high expression syndrome and longer incubation periods. Next, we did the transmission experiment form patients with sporadic CJD (codon 129 Val/Met genotype), dura-associated CJD (codon 129 Met/Met genotype). Among these transmission studies, we recognized that a special type of dura-associated CJD showed unsuccessful transmission even after 360 days' incubation. Therefore, not only with the clinicopathological changes, but also with the transmission experiment, we identified a distinct type of dura-associated CJD with many florid plaques as seen in patients with new variant CJD in United Kingdom.
|
