scholarly journals Strain Fidelity of Chronic Wasting Disease upon Murine Adaptation

2006 ◽  
Vol 80 (24) ◽  
pp. 12303-12311 ◽  
Author(s):  
Christina J. Sigurdson ◽  
Giuseppe Manco ◽  
Petra Schwarz ◽  
Pawel Liberski ◽  
Edward A. Hoover ◽  
...  
Keyword(s):  
North America ◽  
Transgenic Mice ◽  
Chronic Wasting Disease ◽  
Amyloid Plaques ◽  
Serial Passage ◽  
Host Factors ◽  
Species Barrier ◽  
Wasting Disease ◽  
Cerebral Amyloid ◽  
Efficient Transmission

ABSTRACT Chronic wasting disease (CWD), a prion disease of deer and elk, is highly prevalent in some regions of North America. The establishment of mouse-adapted CWD prions has proven difficult due to the strong species barrier between mice and deer. Here we report the efficient transmission of CWD to transgenic mice overexpressing murine PrP. All mice developed disease 500 ± 62 days after intracerebral CWD challenge. The incubation period decreased to 228 ± 103 days on secondary passage and to 162 ± 6 days on tertiary passage. Mice developed very large, radially structured cerebral amyloid plaques similar to those of CWD-infected deer and elk. PrPSc was detected in spleen, indicating that murine CWD was lymphotropic. PrPSc glycoform profiles maintained a predominantly diglycosylated PrP pattern, as seen with CWD in deer and elk, across all passages. Therefore, all pathological, biochemical, and histological strain characteristics of CWD appear to persist upon repetitive serial passage through mice. These findings indicate that the salient strain-specific properties of CWD are encoded by agent-intrinsic components rather than by host factors.

scholarly journals Electron microscopic and confocal laser microscopy analysis of amyloid plaques in chronic wasting disease transmitted to transgenic mice

Prion ◽  
2017 ◽  
Vol 11 (6) ◽  
pp. 431-439
Author(s):  
Beata Sikorska ◽  
Agata Gajos ◽  
Andrzej Bogucki ◽  
Emil Zielonka ◽  
Christina Sigurdson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Chronic Wasting Disease ◽  
Amyloid Plaques ◽  
Confocal Laser Microscopy ◽  
Confocal Laser ◽  
Electron Microscopic ◽  
Wasting Disease ◽  
Laser Microscopy ◽  
Microscopy Analysis

scholarly journals Generation of human chronic wasting disease in transgenic mice

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zerui Wang ◽  
Kefeng Qin ◽  
Manuel V. Camacho ◽  
Ignazio Cali ◽  
Jue Yuan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Species Barrier ◽  
Wasting Disease ◽  
Bona Fide

AbstractChronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

scholarly journals Transmission of Prions from Mule Deer and Elk with Chronic Wasting Disease to Transgenic Mice Expressing Cervid PrP

2004 ◽  
Vol 78 (23) ◽  
pp. 13345-13350 ◽  
Author(s):  
Shawn R. Browning ◽  
Gary L. Mason ◽  
Tanya Seward ◽  
Mike Green ◽  
Gwyneth A. J. Eliason ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Amyloid Plaques ◽  
Neurological Dysfunction ◽  
Wasting Disease ◽  
Prion Strain ◽  
Spongiform Degeneration ◽  
Transmission Studies

ABSTRACT We generated mice expressing cervid prion protein to produce a transgenic system simulating chronic wasting disease (CWD) in deer and elk. While normal mice were resistant to CWD, these transgenic mice uniformly developed signs of neurological dysfunction ∼230 days following intracerebral inoculation with four CWD isolates. Inoculated transgenic mice homozygous for the transgene array developed disease after ∼160 days. The brains of sick transgenic mice exhibited widespread spongiform degeneration and contained abnormal prion protein and abundant amyloid plaques, many of which were florid plaques. Transmission studies indicated that the same prion strain caused CWD in the analyzed mule deer and elk. These mice provide a new and reliable tool for detecting CWD prions.

scholarly journals Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose

2021 ◽  
Author(s):  
Jonathan D F Wadsworth ◽  
Susan Joiner ◽  
Jacqueline M Linehan ◽  
Kezia Jack ◽  
Huda Al-Doujaily ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Brain Tissue ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Zoonotic Potential ◽  
Wasting Disease ◽  
Human Prion Protein ◽  
Prion Transmission ◽  
Wild Reindeer

Abstract Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.

scholarly journals Efficient In Vitro Amplification of Chronic Wasting Disease PrPRES

2007 ◽  
Vol 81 (17) ◽  
pp. 9605-9608 ◽  
Author(s):  
Timothy D. Kurt ◽  
Matthew R. Perrott ◽  
Carol J. Wilusz ◽  
Jeffrey Wilusz ◽  
Surachai Supattapone ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Body Fluids ◽  
The Body ◽  
Wasting Disease ◽  
Highly Efficient ◽  
Significant Step

ABSTRACT Chronic wasting disease (CWD) of cervids is associated with conversion of the normal cervid prion protein, PrPC, to a protease-resistant conformer, PrPCWD. Here we report the use of both nondenaturing amplification and protein-misfolding cyclic amplification (PMCA) to amplify PrPCWD in vitro. Normal brains from deer, transgenic mice expressing cervid PrPC [Tg(cerPrP)1536 mice], and ferrets supported amplification. PMCA using normal Tg(cerPrP)1536 brains as the PrPC substrate produced >6.5 × 109-fold amplification after six rounds. Highly efficient in vitro amplification of PrPCWD is a significant step toward detection of PrPCWD in the body fluids or excreta of CWD-susceptible species.

Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice

2002 ◽  
Vol 20 (11) ◽  
pp. 1147-1150 ◽  
Author(s):  
Jiri G. Safar ◽  
Michael Scott ◽  
Jeff Monaghan ◽  
Camille Deering ◽  
Svetlana Didorenko ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Bovine Spongiform Encephalopathy ◽  
Chronic Wasting Disease ◽  
Spongiform Encephalopathy ◽  
Wasting Disease

scholarly journals Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America

2020 ◽  
Vol 117 (49) ◽  
pp. 31417-31426 ◽  
Author(s):  
Romolo Nonno ◽  
Michele A. Di Bari ◽  
Laura Pirisinu ◽  
Claudia D’Agostino ◽  
Ilaria Vanni ◽  
...  
Keyword(s):  
North America ◽  
North American ◽  
Rangifer Tarandus ◽  
Chronic Wasting Disease ◽  
Strain Differences ◽  
Myodes Glareolus ◽  
Wasting Disease ◽  
Proximate Cause ◽  
Bank Voles ◽  
Regional Deposition

Chronic wasting disease (CWD) is a relentless epidemic disorder caused by infectious prions that threatens the survival of cervid populations and raises increasing public health concerns in North America. In Europe, CWD was detected for the first time in wild Norwegian reindeer (Rangifer tarandus) and moose (Alces alces) in 2016. In this study, we aimed at comparing the strain properties of CWD prions derived from different cervid species in Norway and North America. Using a classical strain typing approach involving transmission and adaptation to bank voles (Myodes glareolus), we found that prions causing CWD in Norway induced incubation times, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and size of their protease-resistant core, different from those that characterize North American CWD. These findings show that CWD prion strains affecting Norwegian cervids are distinct from those found in North America, implying that the highly contagious North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases. In addition, Norwegian CWD isolates showed an unexpected strain variability, with reindeer and moose being caused by different CWD strains. Our findings shed light on the origin of emergent European CWD, have significant implications for understanding the nature and the ecology of CWD in Europe, and highlight the need to assess the zoonotic potential of the new CWD strains detected in Europe.

scholarly journals Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
S. Jo Moore ◽  
M. Heather West Greenlee ◽  
Naveen Kondru ◽  
Sireesha Manne ◽  
Jodi D. Smith ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Mouse Bioassay ◽  
Lymphoid Tissues ◽  
Species Barrier ◽  
Wasting Disease ◽  
Disease Agent ◽  
Domestic Swine

ABSTRACT Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (“market weight” groups). The remaining pigs (“aged” groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

scholarly journals Transmission and Adaptation of Chronic Wasting Disease to Hamsters and Transgenic Mice: Evidence for Strains

2007 ◽  
Vol 81 (8) ◽  
pp. 4305-4314 ◽  
Author(s):  
Gregory J. Raymond ◽  
Lynne D. Raymond ◽  
Kimberly D. Meade-White ◽  
Andrew G. Hughson ◽  
Cynthia Favara ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Wasting Disease ◽  
Incubation Periods

ABSTRACT In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

Sign in / Sign up

Export Citation Format

Share Document