NR AUYH
AU Furuya,K.; Kawahara,N.; Yamakawa,Y.; Kishida,H.; Hachiya,N.S.; Nishijima,M.; Kirino,T.; Kaneko,K.
TI Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation
QU Neuroscience Letters 2006 Jul 24; 402(3): 222-6
PT journal article
AB We have developed a novel procedure in which a small collagen sheet (3 mm x 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.
MH Animals; Catheters, Indwelling; Collagen; Creutzfeldt-Jakob Syndrome/*metabolism/prevention & control/transmission; *Disease Models, Animal; Dura Mater/*transplantation; Genes, Dominant; *Iatrogenic Disease; Infusion Pumps; Injections, Intraventricular; Mice; Mice, Transgenic; Mutation; Osmosis; PrPc Proteins/antagonists & inhibitors; Prions/*administration & dosage/genetics; Recombinant Proteins/administration & dosage/genetics; Research Support, Non-U.S. Gov't
AD Department of Neurosurgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. furuya-nsu@umin.ac.jp
SP englisch
PO Irland