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in vitro prion protein conversion suggests risk of bighorn sheep (ovis canadensis) to transmissible spongiform encephalopathies.transmissible spongiform encephalopathies (tses) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; cwd). the geographical range of bighorn sheep (ovis canadensis; bhs) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of cwd in cervids. no tses have been documented in bhs, but the susceptibility of this species to tses remains unknown.201323938169
comparison of brain prpd distribution in ovine bse and scrapie.scrapie and bovine spongiform encephalopathy (bse) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. surveillance of the bse agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. in our study, using immunohistochemistry (ihc), we assessed the distribution of prp(d) in the brains of 2 experimentally bse-infecte ...201121245284
prpsc spreading patterns in the brain of sheep linked to different prion types.abstract: scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (bse) and creutzfeldt-jakob disease in humans. according to the prion hypothesis, the pathological isoform (prpsc) of the cellular prion protein (prpc) comprises the essential, if not exclusive, component of the transmissible agent. currently, two types of scrapie disease are known - classical and atypic ...201121324114
atypical/nor98 scrapie infectivity in sheep peripheral tissues.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. how ...201121347349
molecular discrimination of sheep bovine spongiform encephalopathy from scrapie.sheep ch1641-like transmissible spongiform encephalopathy isolates have shown molecular similarities to bovine spongiform encephalopathy (bse) isolates. we report that the prion protein prpsc from sheep bse is extremely resistant to denaturation. this feature, combined with the n-terminal prpsc cleavage, allowed differentiation of classical scrapie, including ch1641-like, from natural goat bse and experimental sheep bse.201121470463
characterization of prnp and sprn coding regions from atypical scrapie cases diagnosed in poland.scrapie, a fatal transmissible spongiform encephalopathy (tse) occurs in two phenotypes: classical and atypical. many authors point out that the polymorphism of three codons (136, 154, 171) of the prnp (prp gene) is associated with a sheep susceptibility to classical scrapie. until now, only one prnp gene variant coding phenylalanine at codon 141 has been found to be associated with atypical scrapie. another recently identified and interesting candidate gene for scrapie susceptibility in sheep i ...201121674189
exosome-producing follicle associated epithelium is not involved in uptake of prpd from the gut of sheep (ovis aries): an ultrastructural study.in natural or experimental oral scrapie infection of sheep, disease associated prion protein (prp(d)) often first accumulates in peyer's patch (pp) follicles. the route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. in a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated prp(d) ...201121789232
assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies.the susceptibility of sheep to scrapie is influenced mainly by the prion protein polymorphisms a136v, r154h, and q171r/h. here we analyzed the ability of protein misfolding cyclic amplification (pmca) to model the genetic susceptibility of sheep to scrapie. for this purpose, we studied the efficiency of brain homogenates from sheep with different prp genotypes to support prp(sc) amplification by pmca using an arq/arq scrapie inoculum. the results were then compared with those obtained in vivo us ...201121680531
Molecular cloning and polymorphism analysis of the prion protein gene in Tan sheep of Ningxia, China.The resistance or susceptibility of sheep to scrapie is associated with polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern China, were determined and variability of the PrP amino acids sequence was analyzed in this study. The Pr ...201121722718
PRNP haplotype and genotype frequencies in Brazilian sheep: Issues for conservation and breeding programs.Polymorphisms of PRNP gene have been strongly correlated to the susceptibility/resistance to scrapie in sheep. Variants at the coding positions 136, 154 and 171 have been the most frequently associated to susceptibility to classical scrapie. The aim of this study was to estimate PRNP haplotype and genotype frequencies in a sample of 1400 sheep from 13 different breeds that are representative of the main production regions in Brazil. A total of four different alleles (ARR, ARQ, AHQ and VRQ) and n ...201121816449
effect of prp genotype and route of inoculation on the ability of discriminatory western blot to distinguish scrapie from sheep bovine spongiform encephalopathy.procedures for discriminating scrapie from bovine spongiform encephalopathy (bse) in sheep are relevant to ascertain whether bse has entered the sheep population. this study was aimed at investigating whether the suitability of an official eu discriminative method is affected by the sheep prp genotype and route of infection.201121994325
BSE: where are we now? 201121965237
experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle.prion diseases or transmissible spongiform encephalopathies (tses) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (tme); chronic wasting disease (cwd) of deer, elk and moose; and bovine spongiform encephalopathy (bse) of cattle. the emergence of bse and its spread to human beings in the form of variant creutzfeldt-jakob disease (vcjd) resulted in interest in susceptibility of cattle to cwd, tme and scrapie. experimental cross-species transmission of tse agents p ...201121908269
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation.ABSTRACT: Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. The purpose of this experiment was to determine susceptibility of white-tailed deer to the agent of scrapie after intracerebral inoculation and to compare clinical signs and lesions to those reported for chronic wasting disease (CWD). Deer (n = 5) were inoculated with 1 mL of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with s ...201121988781
heart rate variability analysis in sheep affected by transmissible spongiform encephalopathies.abstract:201122168827
prpsc detection in formalin-fixed paraffin-embedded tissue by elisa.abstract:201122018205
immunophenotype of cells within cervine rectoanal mucosa-associated lymphoid tissue and mesenteric lymph nodes.rectoanal mucosa-associated lymphoid tissue (ramalt) is a part of the lymphoid system that can be sampled easily in live animals, especially ruminants. ramalt biopsy is useful for the diagnosis of transmissible spongiform encephalopathies, including scrapie in sheep and goats and chronic wasting disease (cwd) in cervids. diagnosis is reliant on detection of abnormal prion protein (prp(d)), which is associated with lymphoid follicles. for enzyme linked immunosorbent assays (elisas) detecting prp( ...201122000034
changes induced by natural scrapie in the calretinin-immunopositive cells and fibres of the sheep cerebellar cortex.calretinin (cr)-immunopositive cells and fibres in the cerebellar cortex (vermal archicerebellum and neocerebellum) of scrapie-affected, arq/arq, rasa aragonesa breed sheep were studied in comparison with healthy, young and aged, arq/arq, rasa aragonesa animals and with manchega breed sheep. the scrapie-affected sheep showed signs of both cellular involution and hypertrophic/hyperimmunoreactive responses in all neuronal subtypes; the distribution of the neuronal subtypes in the archi- and neocer ...201122116659
prionemia and leuco-platelet associated infectivity in sheep tse models.the dynamics of the circulation and distribution of transmissible spongiform encephalopathy (tse) agents in the blood of infected individuals remain largely unknown. this clearly limits the understanding of role of blood in tse pathogenesis and the development of reliable tse blood detection assay.using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia. this ability to transmit disease by blood transfusion was ...201122156536
Mechanisms of prion disease progression: a chemical reaction network approach.Fatal neurodegenerative diseases such as bovine spongiform encephalopathy in cattle, scrapie in sheep and Creutzfeldt-Jakob disease in humans are caused by prions. Prion is a protein encoded by a normal cellular gene. The cellular form of the prion, namely PrP(C), is benign but can be converted into a disease-causing form (named scrapie), PrP(Sc), by a conformational change from -helix to -sheets. Prions replicate by this conformational change; that is, PrP(Sc) interacts with PrP(C) producing a ...201122129030
Methodology Adaptation of a low-cost medium-throughput genotyping system for ovine prion protein gene polymorphims associated with scrapie.Resistance and susceptibility to scrapie in sheep have been associated with SNPs located at codons 136, 154 and 171 of the prion protein (PRNP) gene. Many countries have sheep breeding programs selecting for resistance to scrapie based on the genotyping of these SNPs. We adapted a fast and robust method for genotyping sheep flocks for these polymorphisms, with reduced costs. Ninety-six samples were genotyped using an adapted SNaPshot PRNP assay, and the results were checked by resequencin ...201122194174
discrepant epidemiological patterns between classical and atypical scrapie in sheep flocks under french tse control measures.the occurrence of secondary cases of atypical and classical scrapie was examined in 340 outbreaks of atypical and 296 of classical sheep scrapie detected in france during active surveillance programmes between 2002 and 2007. the prevalence of atypical scrapie in these flocks was 0.05% under selective culling and 0.07% under intensified monitoring i.e. not significantly different from that detected during active surveillance of the general population (p>0.5), whereas these figures were much highe ...201019635675
identification of polymorphisms in the ovine shadow of prion protein (sprn) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie.shadow of prion protein (sprn) is an interesting candidate gene thought to be involved in prion pathogenesis. in humans, an association has already been discovered between mutations in sprn and the incidence of variant and sporadic creutzfeldt-jakob disease. however, in sheep, the effect of mutations in sprn is largely unknown. therefore, we analysed the presence of mutations in the entire ovine sprn gene, their association with scrapie susceptibility and their effect on sprn promoter activity. ...201019917049
infection of cell lines with experimental and natural ovine scrapie agents.mouse bioassay remains the gold standard for determining proof of infectivity, strain type, and infectious titer estimation in prion disease research. the development of an approach using ex vivo cell-based assays remains an attractive alternative, both in order to reduce the use of mice and to hasten results. the main limitation of a cell-based approach is the scarcity of cell lines permissive to infection with natural transmissible spongiform encephalopathy strains. this study combines two adv ...201020032176
putative emergence of classical scrapie in a background of enzootic atypical scrapie.active transmissible spongiform encephalopathy (tse) surveillance in small ruminants across europe was implemented in 2002 following the epizootic of bovine spongiform encephalopathy. here, we report the potential emergence of classical scrapie in portugal, in a background of enzootic atypical scrapie. between 2003 and 2008, 375,459 small ruminants were screened in total, with 328 animals confirmed positive for nor98 atypical scrapie. during this period, the prevalence rate of atypical scrapie f ...201020164262
a novel anti-prion protein monoclonal antibody and its single-chain fragment variable derivative with ability to inhibit abnormal prion protein accumulation in cultured cells.mabs t1 and t2 were established by immunizing prp gene ablated mice with recombinant moprp of residues 121-231. both mabs were cross-reactive with prp from hamster, sheep, cattle and deer. a linear epitope of mab t1 was identified at residues 137-143 of moprp and buried in prp(c) expressed on the cell surface. mab t1 showed no inhibitory effect on accumulation of prp(sc) in cultured scrapie-infected neuroblastoma (scn2a) cells. in contrast, mab t2 recognized a discontinuous epitope ranged on, or ...201020377745
fluorescence spectroscopy of the retina for diagnosis of transmissible spongiform encephalopathies.the feasibility of exploiting fluorescence spectra of the eye for diagnosis of transmissible spongiform encephalopathies (tses) was examined. retinas from scrapie-positive sheep were compared with scrapie-negative sheep using fluorescence spectroscopy, and distinct differences in the fluorescence intensity and spectroscopic signatures were observed. the characteristic fluorescent signatures are thought to be the result of an accumulation of lipofuscin in the retina. it appears that the eye, in p ...201020411920
identification of atypical scrapie in canadian sheep.scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant-producing countries of the world. a novel form of this disease was recently recognized and is known by various names, including nor98, nor98-like, and atypical scrapie. differing from classic scrapie in epidemiology, histopathology, and biochemical characteristics, atypical scrapie cases have been identified throughout europe and in the united states. enhanced scrapie surveillance efforts recentl ...201020453215
risk of escape of prions in gaseous emissions from on-farm digestion vessels. 201020605957
digestion and transportation of bovine spongiform encephalopathy-derived prion protein in the sheep intestine.bovine spongiform encephalopathy (bse) is acquired orally and the mechanisms involved in the absorption and transportation of infectivity across the gut wall are therefore critical. isolated gut loops were created in lambs, massaged to remove intestinal contents (flushed) or left non-flushed, inoculated with cattle bse homogenate and excised at different time-points. gut loops were examined by immunohistochemistry (ihc) for disease-associated prion protein (prp(d)), and the contents were analyse ...201020826616
marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model.prion strains yield specific neuropathological features including spongiform degeneration and deposition patterns of pathological prion protein. their invariant regional distribution, following variations in the infection route, has led to the proposal that prions replicate preferentially in defined neuro-anatomical areas. the molecular mechanisms underlying this apparent strain-specific neuronal tropism are currently unknown. however, a possible explanation may be that prion replication is rela ...201020875860
evaluation of the possible transmission of bse and scrapie to gilthead sea bream (sparus aurata).in transmissible spongiform encephalopathies (tses), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (prp(sc)) of the host-encoded cellular prion protein (prp(c)). while the precise mechanism of the prp(c) to prp(sc) conversion is not understood, it is clear that host prp(c) expression is a prerequisite for effective infectious prion propagation. although there have been many stud ...200919636413
frequent missense and insertion/deletion polymorphisms in the ovine shadoo gene parallel species-specific variation in prp.the cellular prion protein prp(c) is encoded by the prnp gene. this protein is expressed in the central nervous system (cns) and serves as a precursor to the misfolded prp(sc) isoform in prion diseases. the prototype prion disease is scrapie in sheep, and whereas prnp exhibits common missense polymorphisms for v136a, r154h and q171r in ovine populations, genetic variation in mouse prnp is limited. recently the cns glycoprotein shadoo (sho) has been shown to resemble prp(c) both in a central hydr ...200919657386
classical sheep scrapie in great britain: spatial analysis and identification of environmental and farm-related risk factors.previous studies suggest that the spatial distribution of classical sheep scrapie in great britain is uneven and that certain flock characteristics may be associated with occurrence of the disease. however, the existence of areas of high and low disease-risk may also result from differences in the spatial distribution of environmental characteristics. in this study we explored the spatial pattern of classical scrapie in great britain between 2002 and 2005 and investigated the association between ...200919737376
prp genotype: a flock-level risk factor for scrapie?previous epidemiological studies of risk factors for classical scrapie at flock level have identified a variety of management and purchase related variables, along with increased flock size and, in some cases, breed effects. although known as a risk factor at the individual animal level, prp genotype frequencies at flock level have not yet been studied. in an unmatched case-control study, three measures of flock-level prion protein (prp) frequency estimates were investigated with respect to the ...200919783057
determination of sex and scrapie resistance genotype in preimplantation ovine embryos.the aim of this study was to test the accuracy of genotype diagnosis after pre-amplification of dna extracted from biopsies obtained by microblade cutting of ovine embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer to recipients. sex and prp genotypes were determined. sex diagnosis was done by pcr amplification of zfx/zfy and sry sequences after pep-pcr while prp genotype determination was performed after specific pre-amplification of specific targ ...200918543282
control of scrapie in the uk sheep population.scrapie is a fatal transmissible spongiform encephalopathy (tse) of sheep, endemic in the uk for centuries. interest in the disease has been heightened over the last decade by the possibility of the related bse being transmissible to and between sheep and a range of control interventions has been proposed and implemented. in this paper, we examined the effect of these policies and their components on observed case rate, susceptible allele frequency and r0 within the framework of a large simulati ...200918687157
serial passage of sheep scrapie inoculum in suffolk sheep.scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. susceptibility to the disease is partly dependent upon the genetic makeup of the host. in a recent study, it was shown that sheep intracerebrally inoculated with a us scrapie agent (no. 13-7) developed scrapie and survived for an average of 19 months post inoculation. in the present study, when this scrapie inoculum was further passaged for 3 successive generations, the survival time was reduced by approximately ...200919112113
field performance of two rapid screening tests in active surveillance of transmissible spongiform encephalopathies in small ruminants.recently, screening tests for monitoring the prevalence of transmissible spongiform encephalopathies specifically in sheep and goats became available. although most countries require comprehensive test validation prior to approval, little is known about their performance under normal operating conditions. switzerland was one of the first countries to implement 2 of these tests, an enzyme-linked immunosorbent assay (elisa) and a western blot, in a 1-year active surveillance program. slaughtered a ...200919139507
prion protein genotypes of italian sheep breeds with lysine-171 and phenylalanine-141 detection.amino acid polymorphisms of the prion protein gene influence sheep susceptibility to classical and atypical scrapie. substitutions at codons 136, 154 and 171 play an important role in classical scrapie. codon 141 leucine to phenylalanine mutation (afrq) has been recognized as an increased risk factor for atypical scrapie. in addition a rare allele with lysine at codon 171 (ark) has been detected in mediterranean sheep breeds. the presence of ark poses two problems: the determination of its frequ ...200919157728
identification of seven haplotypes of the caprine prp gene at codons 127, 142, 154, 211, 222 and 240 in french alpine and saanen breeds and their association with classical scrapie.in sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the prp gene. in goats, there are to date few data related to scrapie susceptibility association with prp gene polymorphisms. in this study, we first investigated prp gene polymorphisms of the french alpine and saanen breeds. based on prp gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. however, only seven haplo ...200919218225
accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host.in order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the vrq allele of the prp gene were infected by the oral route. infection occurred in all lambs with a remarkably short and highly consistent incubation period of approximately 6 months. challenge of lambs at approximately eight months of age resulted in disease in all animals, but with more variable incubation periods aver ...200919243608
ileal tract and peyer's patch innervation in scrapie-free versus scrapie-affected ovines.ileal peyer's patches (pps) are involved early during sheep scrapie infection. this study qualitatively and semi-quantitatively evaluated ileal tract and pp innervation in 29 sarda ovines of different age, prp genotype and scrapie status. a prominent network of fibres was detected within pps, mainly located in interfollicular lymphoid and stromal components. intrafollicular fibres were rarely observed, with no apparent differences between scrapie-free and scrapie-affected animals, or among ovine ...200919330284
failure to detect the presence of prions in the uterine and gestational tissues from a gravida with creutzfeldt-jakob disease.the vertical transmission of a prion disease from infected mothers to their offspring is believed to be one of the routes for the natural spread of animal prion diseases. supporting this notion is the observation that prion infectivity occurs in the placenta of infected ewes. furthermore, the prion protein (prp), both in its cellular form (prp(c)) and its pathological isoform (prp(sc)), has been observed at the fetal-maternal interface of scrapie-infected sheep. however, whether these features o ...200919349373
identification of proteins co-purifying with scrapie infectivity.prp(c), the cellular isoform of prion protein, is widely expressed in most tissues. despite its involvement in several bioprocesses it still has no apparent physiological role. during propagation of transmissible spongiform encephalopathies, prp(c) is converted to the pathological isoform, prp(sc), in a process believed to be mediated by unknown host factors. prp(sc) has altered biochemical properties and forms amyloid aggregates that display infectious characteristics. prp(sc) is also the major ...200919367687
prnp haplotype distribution in moroccan goats.susceptibility/resistance to scrapie in sheep and goats is influenced by host prion protein gene (prnp) genotype. in this study, we report the analysis of prion protein gene polymorphisms in 137 goats of two moroccan populations: d'man and chaouni. we found seven previously described amino acid polymorphisms at codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent mutations. in addition, we identified three new allelic variants: 101r and 139s in d'man goats and 145d in d'man ...200919397523
comparison of strategies for substantiating freedom from scrapie in a sheep flock.the public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led european animal health authorities to launch large screening and genetic selection programmes. if demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. in this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapi ...200919405956
surround optical fiber immunoassay (sofia): an ultra-sensitive assay for prion protein detection.we describe the development of a new technology (sofia) and demonstrate its utility by establishing a sensitive and specific assay for prp(sc). sofia is a surround optical fiber immunoassay which is comprised of a set of specific monoclonal antibodies and comprehensive capture of high energy fluorescence emission. in its current format, this system is capable of detecting less than 10 attogram (ag) of hamster, sheep and deer recombinant prp. approximately 10 ag of prp(sc) from 263 k-infected ham ...200919442839
immunohistochemical characterisation of classical scrapie neuropathology in sheep.neuroinflammation elicited by prp(res) (resistant prion protein [prp]) deposits in the central nervous system (cns) has been shown to involve cellular and oxidative stress responses in bovine spongiform encephalopathy (bse) as well as in several murine models of transmissible spongiform encephalopathy (tse). additionally, deregulation of water homeostasis has been suggested to be a further component of the spongiform changes observed in tses. the aim of the present study was to characterize the ...200919515381
failure to transmit scrapie infection by transferring preimplantation embryos from naturally infected donor sheep.the objective of the study was to examine whether or not the preimplantation embryo can act as a carrier of classic scrapie infection. the study was carried out on quarantined premises with sheep of highly susceptible scrapie genotypes. uninfected embryos, collected from new zealand-derived suffolk ewes, were surgically transferred into recipient ewes that were also of new zealand origin. seventeen negative control lambs were born on the study premises from these embryo transfers. thirty-nine ex ...200919604572
characterization of a us sheep scrapie isolate with short incubation time.scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. susceptibility to the disease is partly dependent upon the genetic makeup of the host. in a previous study it was shown that sheep intracerebrally inoculated with us scrapie inoculum (no. 13-7) developed terminal disease within an average of 19 months. we have since produced an inoculum, no. x124 from pooled brains of us-origin sheep scrapie, that results in incubations nearly threefold shorter. the present stud ...200919605918
spatial distribution of the active surveillance of sheep scrapie in great britain: an exploratory analysis.this paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in great britain. we investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 - 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). we mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled b ...200919607705
tse pathogenesis in cattle and sheep.many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (tse). only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (bse) and scrapie in their natural hosts. in this review, we summarize the most recent insights into the pathogenesis of bse and scrapie starting from the initial uptake of tse agents and crossing of the gut epithelium. following replication in the gut-associated lymphoid tissues (galt), ...200818258167
binding of 14-3-3 proteins to a single stranded oligodeoxynucleotide aptamer.a synthetic library of ca. 10(13) single stranded oligodeoxynucleotides, each comprising a randomized 40mer sequence and homogeneous 10mer flanking regions, was screened for binding to recombinant human 14-3-3gamma. a single aptamer, which showed similar affinities (k(d) approximately 10(-8)m) for six isoforms of the protein, has been shown to bind to undenatured 14-3-3 protein in the cerebral spinal fluid of scrapie infected sheep.200818279908
copper-induced structural changes in the ovine prion protein are influenced by a polymorphism at codon 112.prion diseases are associated with conformational change in the copper-binding protein prp. the copper-binding sites in prp are located in the n-terminal region of the molecule and comprise a series of tandem repeats of the sequence phgggwgq together with two histidines at residues 96 and 111 (human prp numbering). the co-ordination of copper ions within the non-octapeptide repeat metal ion-binding site involves met109 (human numbering, which corresponds with met112 in ovine prp) and the binding ...200818280261
the evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep.the eu commission issued a regulation in 2003, which requires all member states to implement a breeding programme for resistance to transmissible spongiform encephalopathies in sheep by selecting for specific alleles of the prion protein (prp) gene. a key concern with regard to this regulation was that the intensive selection programmes, designed to increase resistance to scrapie, may have a negative impact on a range of other economically important production, reproduction, and disease traits i ...200818284907
a real-time polymerase chain reaction assay to detect single nucleotide polymorphisms at codon 171 in the prion gene for the genotyping of scrapie susceptibility in sheep.the objective of this study was to report a reliable real-time polymerase chain reaction assay compatible with the roche lightcycler 2.0 capable of genotyping sheep for scrapie susceptibility at codon 171. the single nucleotide polymorphisms (snps) in the prion protein gene in sheep that may govern resistance to scrapie at codon 171 encode for lysine (k), histidine (h), glutamine (q), and arginine (r). a modified proteinase k method for leukocytes or whole blood was used to isolate genomic dna f ...200818319434
occurrence and cellular localization of prpd in kidneys of scrapie-affected sheep in the absence of inflammation.following a preliminary description of disease-associated prion protein (prpd) deposition in the kidneys of scrapie-affected sheep, detailed studies have been undertaken in order to evaluate the factors that could account for such prpd accumulation and to determine the precise location of prpd in the renal papillae. immunohistochemical (ihc) examinations for prpd were conducted in kidneys collected at post-mortem from 30 naturally and 37 experimentally infected sheep. in addition, prpd detection ...200818381605
rapid typing of transmissible spongiform encephalopathy strains with differential elisa.the bovine spongiform encephalopathy (bse) agent has been transmitted to humans, leading to variant creutzfeldt-jakob disease. sheep and goats can be experimentally infected by bse and have been potentially exposed to natural bse; however, whether bse can be transmitted to small ruminants is not known. based on the particular biochemical properties of the abnormal prion protein (prpsc) associated with bse, and particularly the increased degradation induced by proteinase k in the n terminal part ...200818394279
myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie.neuroinvasion of the enteric nervous system by prions is an important step in dissemination to the brain, yet very little is known about the basic process of enteric neuroinvasion. using an alimentary model of neonatal disease transmission, neuroinvasion by scrapie prions in the ileum of lambs was detected by immunohistochemical staining for the disease-associated form of the prion protein, prpsc. odds ratios (or) were determined for the frequency of prpsc staining within enteric somata categori ...200818427817
impact of strong selection for the prp major gene on genetic variability of four french sheep breeds(open access publication).effective selection on the prp gene has been implemented since october 2001 in all french sheep breeds. after four years, the arr "resistant" allele frequency increased by about 35% in young males. the aim of this study was to evaluate the impact of this strong selection on genetic variability. it is focussed on four french sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3-4 ye ...200818990357
lions and prions and deer demise.contagious prion diseases--scrapie of sheep and chronic wasting disease of several species in the deer family--give rise to epidemics that seem capable of compromising host population viability. despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration.200819107193
glutathione peroxidase (gpx) activity in blood of ewes on farms in different scrapie categories in iceland.preliminary studies indicated decreased glutathione peroxidase (gpx) activity in blood of ewes on scrapie-afflicted farms. other studies have shown decreased gpx activity in brain of prion-infected mice and in prion-infected cells in vitro. the aim of this study was to examine the gpx activity in blood as well as the distribution of gpx-activity levels from ewes on farms in scrapie-afflicted areas in iceland.200818573202
lack of prp(sc) immunostaining in intracranial ectopic lymphoid follicles in a sheep with concomitant non-suppurative encephalitis and nor98-like atypical scrapie: a case report.during active surveillance for transmissible spongiform encephalopathies (tses) in sheep, an initial reactor was detected using a rapid test on a brain sample. immunohistochemistry confirmed an atypical tse presentation that closely resembled the previously described nor98 cases. sequencing of the prnp gene confirmed the arq/ahq genotype with the l141f mutation at codon 141 associated with this phenotype. the head, including the brain and cranial lymphoid tissues, was sampled and examined thorou ...200817574883
the importance of the prp genotype in active surveillance for ovine scrapie.surveillance activities for ovine scrapie have expanded in the 21st century, following concerns about the potential for a hidden epidemic of bovine spongiform encephalopathy in european sheep populations. large-scale surveys have been used to estimate the prevalence of scrapie infection. in this study we analyse data from the surveys in great britain between 2002 and 2004. when we estimate genotype-specific prevalences for each of the two screening tests used a difference is observed. one test u ...200817588284
immunohistochemistry for prpsc in natural scrapie reveals patterns which are associated with the prp genotype.immunohistochemistry for prpsc is used widely in scrapie diagnosis. in natural scrapie cases the use of immunohistochemistry (ihc) has revealed the existence of up to 12 different morphological types of immunostained deposits. the significance of this pattern variability in relation to genotype has not been studied extensively in natural disease. in this study we recorded in detail prpsc patterns at the obex level of the medulla oblongata from 163 animals derived from 55 flocks which presented t ...200717617872
prpc does not mediate internalization of prpsc but is required at an early stage for de novo prion infection of rov cells.we have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing prpc protein and permissive to infection by a sheep scrapie agent. we demonstrate that abnormal prp (prpsc) and prion infectivity are efficiently internalized in rov cells, whether or not prpc is expressed. at odds with earlier studies implicating cellular heparan sulfates in prpsc internalization, we failed to find any involvement of such molecules in rov cells, indicating that prions can ente ...200717626095
nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity.prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the cns of the protease-resistant prion protein (prpres), a structurally misfolded isoform of its physiological counterpart prpsen. both neuropathogenesis and prion infectivity are related to prpres formation. here, we report that the nonpsychoactive cannabis constituent cannabidiol (cbd) inhibited prpres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related ...200717804615
effectiveness of capillary electrophoresis fluoroimmunoassay of blood prpsc for evaluation of scrapie pathogenesis in sheep.management of prion diseases in livestock would benefit greatly from availability of a validated blood test. a promising immunocapillary electrophoresis technique (also known as capillary electrophoresis fluoroimmunoassay) to detect abnormal prion protein in blood from live sheep is evaluated here. capillary electrophoresis fluoroimmunoassay was applied to analysis of extracted blood from scrapie-exposed sheep (n = 87; 347 samples) at various stages of incubation, and to control sheep (n = 194; ...200717823402
intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep.prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by transmissible spongiform encephalopathy (tse). the presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated prp(sc). we collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of prp(sc) from distinct, ...200717848990
enteroglial and neuronal involvement without apparent neuron loss in ileal enteric nervous system plexuses from scrapie-affected sheep.the enteric nervous system (ens) probably plays a dominant role in sheep scrapie pathogenesis, but little is known about the cell types involved. we investigated the ileal myenteric and submucosal plexuses of four naturally and four orally experimentally scrapie-affected arq/arq sarda sheep, as well as those of 12 healthy-control sarda sheep carrying different prp genotypes. all scrapie-affected animals, euthanized at clinical-disease end stage, showed prpd deposition within enteric glial cells ...200717872545
il-1 family members as candidate genes modulating scrapie susceptibility in sheep: localization, partial characterization, and expression.scrapie (sc) is a transmissible spongiform encephalopathy (tse) in sheep and goats. susceptibility to this neurodegenerative disease is controlled mainly by point mutations at the prnp locus. other genes, apart from prnp, have been reported to modulate resistance/susceptibility to sc. on the basis of several studies on alzheimer's disease and different tse models, and of requirement for correct homeostasis of cytokines in brain, il1b and il1rn were chosen as putative positional and functional ca ...200717242860
microsatellites mcma53 and mcma16 on oar15 are associated with susceptibility to atypical scrapie. 200717257201
species-specificity of a panel of prion protein antibodies for the immunohistochemical study of animal and human prion diseases.monoclonal antibodies to the prion protein (prp) have been of critical importance in the neuropathological characterization of prp-related disease in men and animals. to determine the influence of species-specific amino-acid substitutions recognized by monoclonal antibodies, and to investigate the immunohistochemical reactivity of the latter, analyses were carried out on brain sections of cattle with bovine spongiform encephalopathy, sheep with scrapie, mice infected with scrapie, and human bein ...200717270205
role of the draining lymph node in scrapie agent transmission from the skin.transmissible spongiform encephalopathies (tses) are neurodegenerative diseases that affect humans and animals. diseases include scrapie in sheep and creutzfeldt-jakob disease in humans. following peripheral exposure, tse agents usually accumulate on follicular dendritic cells (fdcs) in lymphoid tissues before neuroinvasion. studies in mice have shown that tse exposure through scarified skin is an effective means of transmission. following inoculation by this route tse agent accumulation upon fd ...200717292972
quantification of peyer's patches in cheviot sheep for future scrapie pathogenesis studies.peyer's patches (pps) are the most probable sites of intestinal uptake of the transmissible spongiform encephalopathy (tse) agent. the amount of pp tissue varies considerably between different age groups of individuals, and whether this variation is related to susceptibility to tse infection raises an intriguing possibility. the purpose of this study was to determine the surface area of pp tissue and the number of associated lymphoid follicles in different age groups of neuropathogenesis unit (n ...200717320972
identification of a proteinase k resistant protein for use as an internal positive control marker in prp western blotting.the routine use of an internal positive control (ipc) marker could prove useful in the diagnosis of transmissible spongiform encephalopathy (tse) diseases, particularly in surveillance programmes where large numbers of negative results are reported. detection of an endogenous ipc protein in a negative sample adds confidence to the correct sample processing throughout the analytical procedure and could avoid the reporting of false negative diagnoses. proteinase k (pk) resistance is one of the key ...200717336356
changes in the expression pattern of the nitrergic system of ovine cerebellum affected by scrapie.the constitutive and inducible isoforms of nitric oxide synthase (nos) and the end-product of nitration, nitrotyrosine, were analyzed by immunohistochemistry, western blotting, and enzymatic activity in sheep at different stages of the prion disease, scrapie. four groups were studied: 1) nonaffected (control), 2) preclinical, 3) clinical, and 4) terminal. constitutive neuronal nos (nnos) was the most abundant isoform present in cerebellar neurons of the sheep. expression of nnos increased in pre ...200717356381
immunological differences between susceptible and resistant sheep during the preclinical phase of scrapie infection.in order to investigate the relationship between the immune response to scrapie infection and genetic susceptibility to the disease in sheep, immune cell subsets and prion protein (prp) expression were determined in susceptible and resistant suffolk sheep in the preclinical phase of infection. at 6 months of age, 12 arq/arq (susceptible) and nine arr/arr (resistant) scrapie-free suffolk lambs were challenged subcutaneously with scrapie inoculum. prefemoral lymphadenectomies were carried out at 1 ...200717374786
atypical scrapie in a swiss goat and implications for transmissible spongiform encephalopathy surveillance.different types of transmissible spongiform encephalopathies (tses) affect sheep and goats. in addition to the classical form of scrapie, both species are susceptible to experimental infections with the bovine spongiform encephalopathy (bse) agent, and in recent years atypical scrapie cases have been reported in sheep from different european countries. atypical scrapie in sheep is characterized by distinct histopathologic lesions and molecular characteristics of the abnormal scrapie prion protei ...200717459826
development of an assay to determine single nucleotide polymorphisms in the prion gene for the genetic diagnosis of relative susceptibility to classical scrapie in sheep.the objective of this study was to develop a reliable taqman 5' nuclease assay for genotyping sheep for scrapie susceptibility. the sheep prion gene contains 2 single nucleotide polymorphisms (snps) that may mediate resistance to classical scrapie, one at codon 136, alanine (a) or valine (v), and another at codon 171, arginine (r) or glutamine (q). the r allele appears to confer resistance to classical scrapie, with the aa(136) rr(171) genotype the most resistant to scrapie and qr(171) only rare ...200717459835
investigation by bioassay of the efficacy of sodium hydroxide treatment on the inactivation of mouse-adapted scrapie.sodium hydroxide (naoh) has been shown to reduce the infectivity of transmissible spongiform encephalopathy (tse) agents. this study investigated the efficacy of sodium hydroxide at 0.1m, 0.25m and 0.5m concentrations for the inactivation of mouse-adapted scrapie strain me7. times and temperatures modelled conditions used in an industrial plasma fractionation plant for sanitisation of ultrafilters, and the sodium hydroxide component of clean in place sanitisation. the concentration of scrapie me ...200717074508
immunological characterization of abnormal prion protein from atypical scrapie cases in sheep using a panel of monoclonal antibodies.after the implementation of an active surveillance programme for scrapie in sheep in the eu, the number of diagnosed classical scrapie cases rose sharply and a novel kind of so-called atypical scrapie case was discovered. these atypical scrapie cases display unusual features concerning the distribution of the abnormal prion protein (prp(sc)) in the brain, a distinct electrophoretic profile of prp(sc) and an inconsistent reaction pattern in the currently used rapid tests. in this report, prp(sc) ...200617098989
infectious agent of sheep scrapie may persist in the environment for at least 16 years.in 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in iceland. affected flocks were culled, premises were disinfected and, after 2-3 years, restocked with lambs from scrapie-free areas. between 1978 and 2004, scrapie recurred on 33 farms. nine of these recurrences occurred 14-21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. of special interest was ...200617098992
transmission of chronic wasting disease of mule deer to suffolk sheep following intracerebral inoculation.to determine the transmissibility of chronic wasting disease (cwd) to sheep, 8 suffolk lambs of various prion protein genotypes (4 arq/arr, 3 arq/arq, 1 arq/vrq at codons 136, 154, and 171, respectively) were inoculated intracerebrally with brain suspension from mule deer with cwd (cwdmd). two other lambs were kept as noninoculated controls. within 36 months postinoculation (mpi), 2 inoculated animals became sick and were euthanized. only 1 sheep (euthanized at 35 mpi) showed clinical signs that ...200617121083
[study on bovine spongiform encephacitis and current status of safety control of medical devices deriving from animals].to introduce the basic information about mad cow disease and the current status of safety control of medical devices derived from mammalian animal tissues.200617191585
ovine infection with the agents of scrapie (ch1641 isolate) and bovine spongiform encephalopathy: immunochemical similarities can be resolved by immunohistochemistry.immunochemical ("rapid") tests, which recognize a partly protease-resistant conformer of the prion protein (prp(res)) are now widely used in europe for the diagnosis of transmissible spongiform encephalopathies (tses). some of these tests can be used to distinguish natural scrapie from experimental bovine spongiform encephalopathy (bse) in sheep, on the basis of migration pattern differences of prp(res) in western immunoblots. however, prp(res) from sheep inoculated with ch1641 scrapie gives an ...200616324707
fewer prpc myeloid-based cells in sheep with the prion-resistant genotype.numerous sheep with the prion gene (prnp) that encodes for 171qq develop scrapie, a neurodegenerative prion disease of sheep. relatively few cases of scrapie-affected sheep with prnp genetics that encode for 171rr, however, have been found. using flow cytometric analysis, statistically fewer prpc-positive microglia and monocytes were observed from sheep with 171rr prnp genetics than from sheep with 171qq prnp genetics (p<0.05). one possibility for the lack of prp(sc) accumulation in brains and l ...200616407757
estimation of the relative risk of developing clinical scrapie: the role of prion protein (prp) genotype and selection bias.prion protein (prp) genotype data from statutory confirmed cases and from three non-case datasets have been used to calculate the odds ratio (or) for the development of clinical scrapie for an individual sheep of a given prp genotype, compared with one possessing the "wild-type" arq/arq genotype. logistic regression has been used to estimate the ors, and a multiple-test procedure has been used to evaluate the statistical significance of each comparison. the results are similar to those observed ...200616415231
breeding programmes for tse resistance in british sheep. i. assessing the impact on prion protein (prp) genotype frequencies.from april 2005, member states of the european union were required to implement a compulsory breeding programme for resistance to transmissible spongiform encephalopathies (tses) in sheep as part of measures to eradicate tses from national flocks. in this paper, we assessed the impact of four different breeding strategies on prion protein (prp) genotype frequencies using a mathematical model which describes in detail gene flow in the british sheep flock. these strategies ranged from the minimum ...200616169614
scrapie infection alters the distribution of plasma metabolites in diseased cheviot sheep indicating a change in energy metabolism.nuclear magnetic resonance (nmr) spectroscopy has been used to profile the metabolic status of plasma from; sheep showing clinical signs of scrapie, those known to be infected with scrapie but yet to show clinical signs, and control animals. the nmr measurements have shown that energy metabolism in scrapie infected animals is altered before the onset of clinical symptoms. these metabolic changes may provide the foundation for a pre-clinical diagnostic test for scrapie in sheep.200616183088
identification of a new leucine haplotype (alq) at codon 154 in the ovine prion protein gene in spanish sheep.genetic susceptibility to scrapie is closely linked to variations at codons 136, 154, and 171 of the prion protein (prnp) gene. this association between the prnp genotype and susceptibility to scrapie is the basis of breeding programs for scrapie resistance in different countries. in this paper, we describe the method used with 2 spanish dairy sheep breeds (churra and castellana) to ascertain the initial status of protection against scrapie as a first step toward adapting their breeding schemes ...200616424251
dna aptamers that bind to prp(c) and not prp(sc) show sequence and structure specificity.dna aptamers were selected against recombinant human (rhu) cellular prion protein (prp(c)) 23-231 by systematic evolution of ligands via a systematic evolution of ligands by exponential (selex) enrichment procedure using lateral flow chromatography. the selex procedure was performed with an aptamer library consisting of a randomized 40-nucleotide core flanked by 28-mer primer-binding sites that, theoretically, represented approximately 10(24) distinct nucleic acid species. sixty nanograms of rhu ...200616446497
short-term study of the uptake of prp(sc) by the peyer's patches in hamsters after oral exposure to scrapie.the disease-associated prion protein (prp(sc)) has been detected in the ileal peyer's patches of lambs as early as one week after oral exposure to scrapie. in hamsters, the earliest reported time of prp(sc) detection in the peyer's patches after oral exposure to scrapie is 69 days post-infection. to evaluate the acute uptake of inoculum and to investigate whether the peyer's patches constitute the primary site of entry for scrapie after oral exposure, hamsters were each exposed orally to 1 ml of ...200616473365
epidemiological analysis of data for scrapie in great britain.in recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (tses) possibly circulating in the sheep population has become a priority in britain and elsewhere in europe. a better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies. here we bound the range of key epidemiological parameters using a combination of relatively detailed pathogenesis and demography data, mo ...200616490141
detection and clinical evolution of scrapie in sheep by 3rd eyelid biopsy.the goal of this article was to characterize the clinical evolution of scrapie in naturally affected sheep. eighteen sheep with scrapie diagnosed by examination of 3rd eyelid biopsy and 12 control ewes were studied throughout the duration of their disease. diagnosis was confirmed postmortem by histopathologic, immunohistochemical, and western blot analysis of nervous tissue. complete clinical examinations were performed every 2 weeks for each animal, of which 3 clinical examinations per animal a ...200616496940
association between incubation time and genotype in sheep experimentally inoculated with scrapie-positive brain homogenate.to compare incubation time and clinical signs of scrapie in codon 136/171 alanine-valine/glutamine-glutamine (avqq) experimentally inoculated sheep with that in sheep with the more common 136/171 aaqq genotype.200616506916
postmortem diagnosis of preclinical and clinical scrapie in sheep by the detection of disease-associated prp in their rectal mucosa.samples of tissue from the central nervous system (cns), the lymphoreticular system (lrs) and the rectal mucosa of a large number of scrapie-exposed sheep, with and without signs of clinical disease, were examined immunohistochemically for evidence of disease-associated prion protein (prp(d)). the rectal mucosa has received almost no attention so far in scrapie diagnosis, despite its abundant rectoanal mucosa-associated lymphoid tissue, and its accessibility. the scrapie-confirmed cases included ...200616531580
gene expression alterations in brains of mice infected with three strains of scrapie.transmissible spongiform encephalopathies (tses) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. examples include creutzfeldt-jakob disease (cjd) in humans, bovine spongiform encephalopathy (bse) in cattle, chronic wasting disease (cwd) in deer and elk, and scrapie in sheep, and experimental mice. to gain insights into tse pathogenesis, we made and used cdna microarrays to identify disease-associated alterations in gene expression. brain ...200616700923
monitoring for bovine spongiform encephalopathy in sheep in great britain, 1998-2004.bovine spongiform encephalopathy (bse) may have been transmitted to british sheep via contaminated feed in the 1980s. strain-typing techniques based on immunohistochemical (ihc) detection of abnormal protein (prp(d)) and the molecular analysis of proteinase-resistant protein (prp(res)) by western blotting (wb) can discriminate between natural or experimental scrapie and experimental bse in sheep. between 1 january 1998 and 31 october 2001, 1247 sheep, clinically suspected of scrapie, were found ...200616760414
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