| Project/Area Number |
16K18790
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Veterinary medical science
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | プリオン / 神経変性疾患 / GPIアンカー / 疾患モデル / 脳神経疾患 |
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| Outline of Final Research Achievements |
A point mutation of methionine to arginine at codon 232 (M232R) of the prion protein (PrP) gene accounts for ~15% of Japanese patients with genetic prion diseases. The pathogenic roles of the M232R mutation in the induction of prion disease have remained elusive because the M232R mutation is located in the C-terminal signal peptide for glycosylphosphatidylinositol (GPI) anchoring that is cleaved off from the mature PrP when the GPI anchor is attached. To elucidate the mechanisms for the induction of prion disease by the M232R mutation, we have performed transmission studies using PrP-humanized knock-in mice carrying the M232R mutation and have investigated the biochemical properties and subcellular localization of the M232R PrP in the present study. The mice expressing the M232R PrP were more susceptible to the transmission of human prion disease. Meanwhile, the expression level, GPI-anchoring, or the subcellular localization of the M232R PrP was not altered.
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