TY  - BOOK
AU  - Furuya,N.
AU  - Kawahara,N.
AU  - Yamakawa,Y.
AU  - Kishida,H.
AU  - Hachiya,N.S.
AU  - Nishijima,M.
AU  - Kirino,T.
AU  - Kirino,T.
TI  - Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation
KW  - IATROGENIC CREUTZFELDT-JAKOB DISEASE (ICJD)
KW  - ANIMAL MODEL OF ICJD
KW  - OSMOTIC PUMP
KW  - HIGHLY PRION-SUSCEPTIBLE TRANSGENIC MICE (TG(MOPRP)4053/FVB)
KW  - DOMINANT NEGATIVE RECOMBINANT PRION PROTEIN (RPRP-Q218K)
N2  - We have developed a novel procedure in which a small collagen sheet (3mm×3 mm)absorbing prion-infected brain homogenates was transplanted onto the brain surface of highly prion-susceptible transgenic mice (Tg(MoPrP)4053/FVB), as an animal model of iatrogenic Creutzfeldt- Jakob disease (iCJD)caused by prion-contaminated cadaveric dura graft transplantation. Using the iCJD model, we further investigated the in vivo efficacy of dominant negative recombinant prion protein with lysine substitution at mouse codon 218 (rPrP-Q218K), which is known to inhibit prion replication in vitro (H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N.S. Hachiya, K. Kaneko, Non-glycosylphosphatidylinositol (GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrPSc replication in vitro, Amyloid, vol. 11, 2004, pp. 14-20.). Following 7-day intracerebroventricular administration of the rPrP-Q218K via an indwelling catheter connected to the implanted osmotic pump, the median incubation period of Tg(MoPrP)4053/FVB was prolonged considerably from 117 days to 131 days (p = 0.016, log-rank test)in the rPrP-Q218K-treated group, even after a lengthy latency period of as long as 30 days by starting the rPrP-Q218K injection. Whether wild-type rPrP, other mutant rPrPs, or the combination of rPrP-Q218K with other anti-prion compounds might extend the survival period in that condition must be further investigated
UR  - https://drive.google.com/file/d/1W6G9-CG5-1i2ByhLe9u6pL_ddhCz_5vB/view?usp=drivesdk
ER  -