| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Research Abstract |
The purpose of this project is to produce the transgenic mouse model that is introduced the nonsense mutation which makes the GPI anchor signal of the prion protein which usually possesses the GPI (Glycosyl Phosphatidyl inositol) anchor invalid reveals the prion protein of secretion type. We already produced the transgenic mouse which designates the codon 231 of the prion protein of the mouse as the stop codon, it has succeeded in the development of the model animal which has many amyloid plaques. As for this secretion type mouse prion protein, in case of the low expression level of the recombinant secretory form, the incubation period after the prion inoculation from 150 days is shortened dramatically on the 90 days, however, in case of the moderate expression level the same as the wild type mouse, it did not become clear for shortening in that incubation period. In addition, although the chimera type gene of the human mouse was introduced, the model animal which reveals the both of GPI type and secretion type had the elongated incubation period, even have the formaiton of amyloid plaques which were similar to the mouse prion protein. Presently, the mouse model which express the both of secretion type and GPI type of complete human type is produced, the shortening effect of the incubation period it is in the midst of observing. Surprisingly, the prion protein of secretion type of the mouse reached the point where the protease resistance which is a hallmark of the conversion of the prion protein is shown. This model is useful to the mechanism elucidation of abnormality conversion of the prion protein. In addition, the secretory form of prion protein enhanced the sensitivity to detect the prion infection in the follicular dendritic cells in the model animals. These findings is followed as the new patent characteristic which presently is in the midst of applying apperared.
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