2007 Fiscal Year Final Research Report Summary
Pathogenesis of BSE and highly sensitive isolation of BSE agent
| Project/Area Number |
17380174
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ONODERA TAKASBI The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor (90012781)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Yoshitsugu The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor (00173922)
SAEKI KEIICHI The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assistant (10311630)
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| Project Period (FY) |
2005 – 2007
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| Keywords | prion / BSE / scrapie / food safety / gene |
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| Research Abstract |
The chain reaction of BSE epidemics in the UK and Europe and subsequent emergence of vCJD in young adults and teenagers have raised concerns and highlighted the importance of risk assessment in the food chain. Recently, several highly sensitive methods for detecting priors have been developed. Representative of these is PMCA.
Originally developed by Claudio Soto and his colleagues, PMCA has been a hot topic of debate in prion meetings all over the world. A broad spectrum of PrP^Sc species have now been successfully amplified using PMCA, including CWD, mouse-adapted scrapie, and BSE. Studies with human sporadic and variant CJD cases show that PMCA amplification efficiency is tightly controlled by the PrP^C substrate genotype at codon 129. PMCA appears to overcome the species barrier encountered during cross-species transmission more rapidly than in vivo. By "forcing" the technique with lower dilutions of the PrP^Sc seed and more amplification rounds, mouse Chandler PrP^Sc can now convert hamster PrP^C or cervid PrP^C, a conversion that might be observable in vivo but only with extremely long incubation periods. Castilla J. showed that using PMCA, PrP^Sc was generated from the healthy brains of 11 different species, including bank voles, mice, cattle, humans, sheep and rabbits, generating a variety of electrophoretic profiles. PMCA was able to detect PrP^Sc in as little as 1 μL of blood from an asymptomatic prion-infected mouse. Given the increasing evidence of human to human transmission via blood products, scientists are waiting for PMCA to be incorporated into a reliable test with the ability to identify blood donors that are asymptomatic carriers. Further advances in amplification technology are to be expected and the replacement of PrP^C by recombinant PrP as a substrate as well as the use of intermittent shaking rather than sonication should circumvent some of the difficulties in the near future.
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