|Budget Amount *help
¥13,100,000 (Direct Cost : ¥13,100,000)
Fiscal Year 1999 : ¥4,300,000 (Direct Cost : ¥4,300,000)
Fiscal Year 1998 : ¥8,800,000 (Direct Cost : ¥8,800,000)
To study the cellular distribution and the mechanism of abnormal conversion of prion protein, we established the transgenic mice with human/mouse chimeric prion protein. Normal cellular form of prion protein in the transgenic mice was easily detected by the immunohistochemical techniques because of high expression level of recombinant prion protein. In the central nervous system, recombinant prion protein was recognized in the axon terminal portion of the neurons. In general organs, we detected recombinant prion protein in the adrenal medulla, the Auerbach's plexus, C cells of the thyroid gland, the anterior pituitary gland, the peripheral nerves, and the myocytes in the heart and the skeletal muscles. We confirmed these recombinant prion protein positive cells were rally prion protein-positive cells in the immunohistochemical analysis with the wild-type mice. In the study of the embryonic state, the cells originated from the neural crest were strongly positive in the prion protein immunolabellings. Among recombinant prion protein-positive cells, we detected the different glycosylation-pattern of prion protein in the Western blot analysis. In the transmission experiment, our animal model was recognized to be a highly sensitive model for human prions. However, it is not possible to detect abnormal isoform of prion protein in general organs except for the central nervous system. Thus, an organ-specific factor to convert the normal cellular form into the abnormal form of prion protein should be clarified in near future.