2007 Fiscal Year Final Research Report Summary
A development for releasing dominant negative pathomechanism on the model of keratin point mutation
| Project/Area Number |
17591169
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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 |
Dermatology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
TANAKA Toshihiro Shiga University of Medical Science, Undergraduate School of Medicine, Professor (50188314)
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| Project Period (FY) |
2005 – 2007
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| Keywords | keratin 9 / point mutation / palmoplamtar hyperkeratosis / congenital bullous disease / hereditary disease |
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| Research Abstract |
We constructed cells having bah the wad type keratin and point mutated keratin. Wild type keratin derived from internal keratin itself and point mutated keratin derived from cDNA construct. Full length cDNA from patient epidermal keratin 9 was constructed into the expression a and subsequently transfected into the cells which has internal keratin (wild type). Also wild type keratin 9 expression vector was constructed and transfected into the cells. Cells transfected with wild type keratin revealed fiber structure whereas cells transfected with point mutated keratin reveals droplet formaed or short formed keratin filaments. These fact reveals that our model reflects abnormality of cell skeleton seen in patient epidermis. Based on this result we permormed an experiment which release the pathomechanism of abonormal keratin formation, because this abonomal morphology came from the dominant negative effect of keratin polimerization. Our strategy of editing point mutated keratin cDNA or promotion of the degeneration of point mutated keratin mRNA was observed in qualitative level but in quantitative level we concluded that it necessary ware in dose response manner. These result suggest that the natural gene therapy, as seen inpatient in the manner that the age goes, the sympton become weaker, are not editing of genme nor depressing the expression level of point mutated mRNA. For overall, our result raised for the research purpose. Moreover, these result suggest the new aspect for the understanding the pathomechanism of hereditary disease.
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