2003 Fiscal Year Final Research Report Summary
Function of transgene structure and its products on conformational changes in transgenic model mice of prion disease
| Project/Area Number |
13680913
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Kyushu University |
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Principal Investigator |
MOHRI Shirou Kyushu University, Graduate School of Medical Sciences, Prof, 大学院・医学研究院, 教授 (40117271)
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| Project Period (FY) |
2001 – 2003
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| Keywords | transgenic mouse / trans gene structure / gene product / conformational change / prion disease |
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| Research Abstract |
Over expression of transgene products by transgenic mouse as a model animal of prion disease would be more advantageous to reproduce abnormal prion protein (PrP) after injection of prion, according to the prion hypothesis. Some strains of transgenic (Tg) mice over expressing with mouse prion or hamster prion have been established as model of high sensitive for prion infection.
To establish a bioassay system for human prions, we made some transgenic mouse models which express with the human-mouse chimeric PrP. Over expressing chimeric prion protein with the transgenic mice, however, did not necessarily change easily the conformation from PrP^C to PrP^<Se>. On the other hand, full length PrP gene to C-terminus expressing over human PrP^C or murine PrP^c with the same tg-vector as the chimeric tg mice were easily change the conformation to PrP^<Sc> affecting the host mice to prion disease. The tg mice expressing full-length PrP^c were more sensitive to prion in proportion to the amount of over expression level.
As the result, Tg mice model of prion disease expressing higher amount of chemeric PrP^C might not apply to the prion hypothesis but tg model mice with full-length PrP^c. This suggests that PrP conformation, produced by PrP gene structure influences the function of changing PrP^C to PrP^<Sc>
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