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Justin J. Greenlee - One of the best experts on this subject based on the ideXlab platform.
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transmission of the atypical nor98 Scrapie agent to suffolk sheep with vrq arq arq arq and arq arr genotypes
PLOS ONE, 2021Co-Authors: Eric D Cassmann, Sylvie L Benestad, Najiba Mammadova, Jo S Moore, Justin J. GreenleeAbstract:Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 Scrapie occurs in sheep that tend to be resistant to classical Scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 Scrapie agent in three genotypes of Suffolk sheep and characterize the distribution of misfolded prion protein (PrPSc). Ten sheep were intracranially inoculated with brain homogenate from a sheep with Atypical/Nor98 Scrapie. All sheep with the ARQ/ARQ and ARQ/ARR genotypes developed Atypical/Nor98 Scrapie confirmed by immunohistochemistry, and one sheep with the VRQ/ARQ genotype had detectable PrPSc consistent with Atypical/Nor98 Scrapie at the experimental endpoint of 8 years. Sheep with mild early accumulations of PrPSc in the cerebellum had concomitant retinal PrPSc. Accordingly, large amounts of retinal PrPSc were identified in clinically affected sheep and sheep with dense accumulations of PrPSc in the cerebellum.
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autoclave treatment of the classical Scrapie agent us no 13 7 and experimental inoculation to susceptible vrq arq sheep via the oral route results in decreased transmission efficiency
PLOS ONE, 2020Co-Authors: Eric D Cassmann, Najiba Mammadova, Justin J. GreenleeAbstract:Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate Scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical Scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US Scrapie strain 13-7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem Scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed Scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrPSc in antemortem rectal biopsies, and two (2/5) other sheep had PrPSc in postmortem rectal tissue. A single sheep (1/5) was positive for Scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed Scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical Scrapie strain 13-7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.
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efficient transmission of classical Scrapie agent x124 by intralingual route to genetically susceptible sheep with a low dose inoculum
Research in Veterinary Science, 2020Co-Authors: Najiba Mammadova, Eric D Cassmann, Justin J. GreenleeAbstract:Abstract Scrapie is a naturally occurring prion disease of sheep and goats that results in accumulation of the misfolded prion protein (PrPSc) and progressive neurodegeneration. After inoculation with classical Scrapie isolate x124, susceptibility and incubation period are associated with valine at codon 136 (V136) of the prion protein: VRQ/VRQ had the shortest incubation periods, followed by VRQ/ARQ sheep, while ARQ/ARQ sheep only developed disease after inoculation via the intracerebral route. Intralingual inoculation of TSE agents effectively transmits disease similar to intracranial inoculation; therefore, it is possible that oral lesions may facilitate susceptibility to Scrapie transmission. In this study, investigated the infectivity of decreasing doses of the x124 Scrapie agent (100 mg, 50 mg, 20 mg, and 10 mg) on incubation time and attack rate after experimental intralingual inoculation into VRQ/ARQ sheep. The lowest inoculum dose tested in this study effectively transmitted the x124 Scrapie agent in VRQ/ARQ sheep with a 100% attack rate and no significant difference in incubation times among sheep inoculated with varying doses. Moreover, immunohistochemistry and western blot analysis revealed similar biochemical and immunohistochemical features among the four cohorts of sheep irrespective of inoculum dose. This study provides a starting point for further investigation to determine the minimum infectious dose of x124 Scrapie in sheep and its effect on attack rate and incubation time, central for assessing the potential risk of Scrapie occurrence in sheep flock.
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Oral inoculation of neonatal Suffolk sheep with the agent of classical Scrapie results in PrP(Sc) accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype.
Research in veterinary science, 2016Co-Authors: Justin J. Greenlee, Jodi D. Smith, Amir N. HamirAbstract:Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the Scrapie agent. This study reports the failure to detect PrP(Sc) in nervous or lymphoid tissues of Suffolk sheep of the PRNP ARQ/ARR genotype after oral inoculation with a U.S. Scrapie isolate. Lambs were inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of Scrapie until they were necropsied at 86 months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of Scrapie infection. Neonatal sheep of the ARQ/ARQ genotype receiving the same inoculum developed Scrapie within 24 months. Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial inoculation develop Scrapie with a prolonged incubation period and with abnormal prion present within the central nervous system, but not peripheral lymphoid tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral infection with the Scrapie isolate used even during the neonatal period.
Adriano Aguzzi - One of the best experts on this subject based on the ideXlab platform.
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prion protein devoid of the octapeptide repeat region restores susceptibility to Scrapie in prp knockout mice
Neuron, 2000Co-Authors: Eckhard Flechsig, Alex Raeber, Marek Fischer, Adriano Aguzzi, Doron Shmerling, Ivan Hegyi, Antonio Cozzio, Christian Von Mering, Charles WeissmannAbstract:Mice devoid of PrP are resistant to Scrapie and fail to replicate the agent. Introduction of transgenes expressing PrP into such mice restores susceptibility to Scrapie. We find that truncated PrP devoid of the five copper binding octarepeats still sustains Scrapie infection; however, incubation times are longer and prion titers and protease-resistant PrP are about 30-fold lower than in wild-type mice. Surprisingly, brains of terminally ill animals show no histopathology typical for Scrapie. However, in the spinal cord, infectivity, gliosis, and motor neuron loss are as in Scrapie-infected wild-type controls. Thus, while the region comprising the octarepeats is not essential for mediating pathogenesis and prion replication, it modulates the extent of these events and of disease presentation.
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normal host prion protein necessary for Scrapie induced neurotoxicity
Nature, 1996Co-Authors: Sebastian Brandner, Stefan Isenmann, Alex Raeber, Marek Fischer, Andreas W Sailer, Charles Weissmann, Yasushi Kobayashi, Silvia Marino, Adriano AguzziAbstract:ACCUMULATION of the prion protein PrPSc, a pathological and protease-resistant isoform of the normal host protein PrPc, is a feature of prion disease such as Scrapie1,2. It is still unknown whether Scrapie pathology comes about by neurotoxicity of PrPSc, acute depletion of PrPc, or some other mechanism. Here we investigate this question by grafting neural tissue overexpressing PrPc into the brain of PrP-deficient mice which are Scrapie-resistant and do not propagate infectivity3–5. After intracerebral inoculation with Scrapie prions, the grafts accumulated high levels of PrPSc and infectivity and developed the severe histopathological changes characteristic of Scrapie. Moreover, substantial amounts of graft-derived PrPSc migrated into the host brain. Even 16 months after inoculation no pathological changes were seen in PrP-deficient tissue, not even in the immediate vicinity of the grafts. Therefore, in addition to being resistant to Scrapie infection, brain tissue devoid of PrPc is not damaged by exogenous PrPSc.
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normal host prion protein necessary for Scrapie induced neurotoxicity
Nature, 1996Co-Authors: Sebastian Brandner, Stefan Isenmann, Alex Raeber, Marek Fischer, Andreas W Sailer, Charles Weissmann, Yasushi Kobayashi, Silvia Marino, Adriano AguzziAbstract:ACCUMULATION of the prion protein PrPSc, a pathological and protease-resistant isoform of the normal host protein PrPc, is a feature of prion disease such as Scrapie1,2. It is still unknown whether Scrapie pathology comes about by neurotoxicity of PrPSc, acute depletion of PrPc, or some other mechanism. Here we investigate this question by grafting neural tissue overexpressing PrPc into the brain of PrP-deficient mice which are Scrapie-resistant and do not propagate infectivity3–5. After intracerebral inoculation with Scrapie prions, the grafts accumulated high levels of PrPSc and infectivity and developed the severe histopathological changes characteristic of Scrapie. Moreover, substantial amounts of graft-derived PrPSc migrated into the host brain. Even 16 months after inoculation no pathological changes were seen in PrP-deficient tissue, not even in the immediate vicinity of the grafts. Therefore, in addition to being resistant to Scrapie infection, brain tissue devoid of PrPc is not damaged by exogenous PrPSc.
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mice devoid of prp are resistant to Scrapie
Cell, 1993Co-Authors: Hansruedi Bueler, Andreas W Sailer, Adriano Aguzzi, R A Greiner, P Autenried, Michel Aguet, Charles WeissmannAbstract:S.B. Prusiner proposed that the infectious agent of scraple, the prion, is PrPSc, a modified form of the normal host protein PrPC. Prn-p0/0 mice devoid of PrPC showed normal development and behavior. When inoculated with mouse Scrapie prions, they remained free of Scrapie symptoms for at least 13 months while wild-type controls all died within 6 months. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to Scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to Scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.
Olivier Andréoletti - One of the best experts on this subject based on the ideXlab platform.
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Classical Scrapie in small ruminants is caused by at least four different prion strains
Veterinary Research, 2021Co-Authors: Alba Marín-moreno, Patricia Aguilar-calvo, Juan Carlos Espinosa, María Zamora-ceballos, José Luis Pitarch, Lorenzo González, Natalia Fernández-borges, Leonor Orge, Olivier Andréoletti, Romolo NonnoAbstract:The diversity of goat Scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical Scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some Scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare Scrapie strains in sheep and goats, sheep Scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical Scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical Scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different Scrapie strains and BSE-C does not support the idea that classical Scrapie is the origin of epidemic BSE-C.
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goat k222 prpc polymorphic variant does not provide resistance to atypical Scrapie in transgenic mice
Veterinary Research, 2016Co-Authors: Patricia Aguilarcalvo, Juan Carlos Espinosa, Lorenzo González, Leonor Orge, Olivier Andréoletti, Ramon A Juste, Juan Maria TorresAbstract:Host prion (PrPC) genotype is a major determinant for the susceptibility to prion diseases. The Q/K222-PrPC polymorphic variant provides goats and mice with high resistance against classical Scrapie and bovine spongiform encephalopathy (BSE); yet its effect against atypical Scrapie is unknown. Here, transgenic mice expressing the goat wild-type (wt) or the K222-PrPC variant were intracerebrally inoculated with several natural cases of atypical Scrapie from sheep and goat and their susceptibility to the prion disease was determined. Goat wt and K222-PrPC transgenic mice were 100% susceptible to all the atypical Scrapie isolates, showing similar survival times and almost identical disease phenotypes. The capacity of the K222-PrPC variant to replicate specifically the atypical Scrapie strain as efficiently as the goat wt PrPC, but not the classical Scrapie or cattle-BSE as previously reported, further suggests the involvement of concrete areas of the host PrPC in the strain-dependent replication of prions.
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atypical nor98 Scrapie infectivity in sheep peripheral tissues
PLOS Pathogens, 2011Co-Authors: Olivier Andréoletti, Sylvie L Benestad, Leonor Orge, Vincent Beringue, Hugh Simmons, Claire Litaise, Stephanie Simon, Annick Le Dur, Hubert Laude, Severine LuganAbstract:Atypical/Nor98 Scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 Scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 Scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 Scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 Scrapie infectivity could remain PrP(Sc) negative. This feature will impact detection of Atypical/Nor98 Scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical Scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.
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identification of new quantitative trait loci other than the prnp gene modulating the Scrapie incubation period in sheep
Genetics, 2008Co-Authors: Carole Moreno, Olivier Andréoletti, Gian Mario Cosseddu, Laurent Schibler, A Roig, Katayoun Moazamigoudarzi, F Eychenne, D Lajous, F Schelcher, E P CribiuAbstract:Although susceptibility to Scrapie is largely controlled by the PRNP gene, we have searched for additional genomic regions that affect Scrapie incubation time in sheep, using two half-sib families with a susceptible PRNP genotype and naturally infected by Scrapie. Quantitative trait loci were detected on OAR6 and OAR18.
Eric D Cassmann - One of the best experts on this subject based on the ideXlab platform.
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transmission of the atypical nor98 Scrapie agent to suffolk sheep with vrq arq arq arq and arq arr genotypes
PLOS ONE, 2021Co-Authors: Eric D Cassmann, Sylvie L Benestad, Najiba Mammadova, Jo S Moore, Justin J. GreenleeAbstract:Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 Scrapie occurs in sheep that tend to be resistant to classical Scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 Scrapie agent in three genotypes of Suffolk sheep and characterize the distribution of misfolded prion protein (PrPSc). Ten sheep were intracranially inoculated with brain homogenate from a sheep with Atypical/Nor98 Scrapie. All sheep with the ARQ/ARQ and ARQ/ARR genotypes developed Atypical/Nor98 Scrapie confirmed by immunohistochemistry, and one sheep with the VRQ/ARQ genotype had detectable PrPSc consistent with Atypical/Nor98 Scrapie at the experimental endpoint of 8 years. Sheep with mild early accumulations of PrPSc in the cerebellum had concomitant retinal PrPSc. Accordingly, large amounts of retinal PrPSc were identified in clinically affected sheep and sheep with dense accumulations of PrPSc in the cerebellum.
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autoclave treatment of the classical Scrapie agent us no 13 7 and experimental inoculation to susceptible vrq arq sheep via the oral route results in decreased transmission efficiency
PLOS ONE, 2020Co-Authors: Eric D Cassmann, Najiba Mammadova, Justin J. GreenleeAbstract:Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate Scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical Scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US Scrapie strain 13-7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem Scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed Scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrPSc in antemortem rectal biopsies, and two (2/5) other sheep had PrPSc in postmortem rectal tissue. A single sheep (1/5) was positive for Scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed Scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical Scrapie strain 13-7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.
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efficient transmission of classical Scrapie agent x124 by intralingual route to genetically susceptible sheep with a low dose inoculum
Research in Veterinary Science, 2020Co-Authors: Najiba Mammadova, Eric D Cassmann, Justin J. GreenleeAbstract:Abstract Scrapie is a naturally occurring prion disease of sheep and goats that results in accumulation of the misfolded prion protein (PrPSc) and progressive neurodegeneration. After inoculation with classical Scrapie isolate x124, susceptibility and incubation period are associated with valine at codon 136 (V136) of the prion protein: VRQ/VRQ had the shortest incubation periods, followed by VRQ/ARQ sheep, while ARQ/ARQ sheep only developed disease after inoculation via the intracerebral route. Intralingual inoculation of TSE agents effectively transmits disease similar to intracranial inoculation; therefore, it is possible that oral lesions may facilitate susceptibility to Scrapie transmission. In this study, investigated the infectivity of decreasing doses of the x124 Scrapie agent (100 mg, 50 mg, 20 mg, and 10 mg) on incubation time and attack rate after experimental intralingual inoculation into VRQ/ARQ sheep. The lowest inoculum dose tested in this study effectively transmitted the x124 Scrapie agent in VRQ/ARQ sheep with a 100% attack rate and no significant difference in incubation times among sheep inoculated with varying doses. Moreover, immunohistochemistry and western blot analysis revealed similar biochemical and immunohistochemical features among the four cohorts of sheep irrespective of inoculum dose. This study provides a starting point for further investigation to determine the minimum infectious dose of x124 Scrapie in sheep and its effect on attack rate and incubation time, central for assessing the potential risk of Scrapie occurrence in sheep flock.
Wilfred Goldmann - One of the best experts on this subject based on the ideXlab platform.
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BSE can propagate in sheep co-infected or pre-infected with Scrapie
'Springer Science and Business Media LLC', 2021Co-Authors: Angela Chong, Lorenzo González, James D. Foster, Wilfred Goldmann, Martin Jeffrey, Matthew J. O’connor, Keith Bishop, Ben C. Maddison, Fiona E. Houston, Kevin C. GoughAbstract:Abstract To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and Scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with Scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with Scrapie after being born into a Scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or Scrapie-like PrPSc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of Scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, Scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant Scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to Scrapie had Scrapie-like incubation periods and dominant Scrapie PrPSc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for Scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental Scrapie did not propagate BSE but VRQ/VRQ sheep with natural Scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrPSc strain in brain tissue. Indeed, for several animals, a dominant Scrapie biochemical phenotype in brain did not preclude the presence of BSE prion
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a cross sectional study of prnp gene in two native sicilian goat populations in italy a relation between prion gene polymorphisms and Scrapie incidence
Journal of Genetics, 2017Co-Authors: Sergio Migliore, Wilfred Goldmann, Stefano Agnello, Salvatore Davola, Vincenzo Di Marco Lo Presti, Maria VitaleAbstract:Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting humans and animals, and Scrapie in small ruminants is considered the archetype of TSEs. Derivata di Siria is a native dairy goat of Sicily (south Italy), which is related to Syrian goat breeds. Scrapie disease is considered endemic in Sicily since 1997, following the administration of an infected vaccine. Derivata di Siria goats were involved in six of 66 Scrapie-infected flocks in Sicily. Prion protein gene (PRNP) analysis revealed that none of the Scrapie cases carried the p.Gln222Lys variant. Sequencing of PRNP in this goat population showed a high frequency (15%) of p.Gln222Lys variant confirming its association with Scrapie resistance. PRNP polymorphisms were also analysed in the population of Pantelleria, a small Sicilian Island, where Scrapie has never been reported. The native goat breed ‘Pantesca’ was maintained up to almost 80 years and the size of the sheep population on this island has historically been very low. Currently, a crossbreed goat population of 253 heads is present on the island. PRNP genotyping of Pantelleria goats showed genetic variation, with low presence of wild-type goats and the lack of protective alleles. These data reinforce the association between PRNP polymorphisms in small ruminants and Scrapie incidence.
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Downloaded from www.microbiologyresearch.org by
2016Co-Authors: Wilfred Goldmann, Hugh FraserAbstract:in previous natural Scrapie transmissions, the results varied between Scrapie sources in terms of the incidence of disease, incubation periods and neuropathology in challenged mice. This contrasted with the uniformity seen in transmissions of BSE to mice. The Scrapie and BSE isolates were characterized further by serial passage in mice. Different TSE strains were isolated from each source according to the Sinc or PrP genotype of the mouse used for passage. The same two mouse-passaged strains, 301C and 301V, were isolated from each of three BSE sources. Despite the variation seen in the primary transmissions of Scrapie, relatively few mouse-passaged Scrapie strains were isolated and these were distinct from the BSE-derived strains. The ME7 Scrapie strain, which has often been isolated from independent sheep sources in the past, was identified in isolates from four of the sheep. However, a new distinct strain, 221C, was derived from a further four Scrapie sheep. These results suggest that there is agent strain variation in natural Scrapie in sheep and that the spectrum of strains present may have changed over the last 20 years. The tested sample is too small to come to any conclusions about whether the BSE strain is present i
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Monitoring of clinical signs in goats with transmissible spongiform encephalopathies
BMC Veterinary Research, 2010Co-Authors: Timm Konold, Lorenzo González, Wilfred Goldmann, Gemma E Bone, Laura J Phelan, Marion M Simmons, Sílvia Sisó, Saira Cawthraw, Steve Ac HawkinsAbstract:Background As there is limited information about the clinical signs of BSE and Scrapie in goats, studies were conducted to describe the clinical progression of Scrapie and BSE in goats and to evaluate a short clinical protocol for its use in detecting Scrapie-affected goats in two herds with previously confirmed Scrapie cases. Clinical assessments were carried out in five goats intracerebrally infected with the BSE agent as well as five reported Scrapie suspects and 346 goats subject to cull from the two herds, 24 of which were retained for further monitoring. The brain and selected lymphoid tissue were examined by postmortem tests for disease confirmation. Results The sensitivity and specificity of the short clinical protocol in detecting a Scrapie case in the Scrapie-affected herds was 3.9% and 99.6%, respectively, based on the presence of tremor, positive scratch test, extensive hair loss, ataxia and absent menace response. All BSE- and Scrapie-affected goats displayed abnormalities in sensation (over-reactivity to external stimuli, startle responses, pruritus, absent menace response) and movement (ataxia, tremor, postural deficits) at an advanced clinical stage but the first detectable sign associated with Scrapie or BSE could vary between animals. Signs of pruritus were not always present despite similar prion protein genotypes. Clinical signs of Scrapie were also displayed by two Scrapie cases that presented with detectable disease-associated prion protein only in lymphoid tissues. Conclusions BSE and Scrapie may present as pruritic and non-pruritic forms in goats. Signs assessed for the clinical diagnosis of Scrapie or BSE in goats should include postural and gait abnormalities, pruritus and visual impairment. However, many Scrapie cases will be missed if detection is solely based on the display of clinical signs. PrP^d accumulation in the brain appeared to be related to the severity of clinical disease but not to the display of individual neurological signs.
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atypical nor98 Scrapie properties of the agent genetics and epidemiology
Veterinary Research, 2008Co-Authors: Sylvie L Benestad, Wilfred Goldmann, Jeannoel Arsac, Maria NoremarkAbstract:Atypical/Nor98 Scrapie cases in sheep were diagnosed for the first time in Norway in 1998. They are now identified in small ruminants in most European countries and represent an increasingly large proportion of the Scrapie cases diagnosed in Europe. Atypical/Nor98 Scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the TSE agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved in classical Scrapie that they have provided a challenging diagnostic for many years. No strain diversity has yet been identified among the atypical/Nor98 Scrapie sample cases. The genetic predisposition of the sheep affected by atypical/Nor98 Scrapie is almost inverted compared to classical Scrapie, and the exact origin of this sporadic TSE strain is still speculative, but a spontaneous, non-contagious origin, like sporadic Creutzfeldt- Jakob disease in humans, can not be excluded. Further transmission and epidemiological studies are needed to better address this hypothesis. atypical Scrapie / Nor98 / transmissible spongiform encephalopathies TSE / genetics / epidemiology
