NR ATHR
AU Matsuura,Y.; Mohri,S.; Ishikawa,Y.; Fujita,Y.; Doiguchi,M.; Kitamoto,T.
TI Conversion of recombinant PrPc to PrPRes in transgenic mice promotes conversion of endogenous mouse PrPc to PrPRes
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-23
PT Konferenz-Poster
AB Transgenic mice expressing a chimeric human/mouse prion protein gene containing methionine at codon 129 (ChM), designated as Tg-ChM mice, have sensitive to some human prions. We examined the conversion effect of prion protein (PrP) from normal form (PrPc) into proteinase resistant form (PrPRes), by inoculating with supernatant of patient brain homogenate of sporadic Creutzfeldt-Jakob disease type 1 MM (H3) to Tg-ChM mice with homozygote, hemizygote, and ablation of mouse prion protein gene (prnp), and non-transgenic (non-Tg) mice. Mean incubation period of H3-transmission to Tg-ChM mice with homozygote and hemizygote of prnp were 382 days and 215 days, respectively, while that to Tg-ChM mice ablated prnp was 156 days. The incubation periods of Tg-ChM mice inoculated with H3 were shortened in proportion to decrease in an amount of the prnp expression. On the other hand, non-Tg mice inoculated with H3 developed no clinical signs at 716 days post inoculation but PrP deposition was slightly shown in the brain by immunohistochemistry. And the PrPRes of mouse PrP (MoPrPRes) in non-Tg mice was rarely detected by western blot analysis following proteinase K digestion. Interestingly, MoPrPRes in Tg-ChM mice with prnp-homozygote inoculated with H3 was definitely detected by western blot analysis, in spite of the shorter incubation period than non-Tg mice. In Tg-ChM mice, conversion-efficient chimeric PrP gave rise to conversion effect on conversion-inefficient MoPrPc to MoPrP Res, while endogenous MoPrPc worked as an inhibitory factor of conversion of induced chimeric PrP to PrPRes.
AD Yuichi Matsuura, Shirou Mohri, Yukiko Ishikawa, Yukitoki Fujita, Masamichi Doiguchi, Kyushu University, Japan; Tetsuyuki Kitamoto, Tohoku University, Japan
SP englisch
PO Deutschland