PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Scrapie”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2000

The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks.

The amino-acid sequence of the PrP protein plays an important role in determining whether sheep are susceptible to scrapie. Although the genetics of scrapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of four UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years and two were scrapie free. Scrapie-resistant PrP genotypes predominated in all flocks but highly susceptible genotypes were present in each case. The distribution of PrP genotypes was similar in the scrapie-affected and scrapie-free flocks. The former, however, showed a slight but significant skew towards more susceptible genotypes despite their previous losses of susceptible sheep. Surprisingly, this skew was apparent in younger, but not older, sheep. We suggest that these patterns may occur if sheep flocks destined to become scrapie affected are predisposed by a genetic profile skewed towards susceptibility. The age structure of the scrapie-affected flocks suggests that the number of losses attributable directly or indirectly to scrapie considerably exceeds that recognized by the farmers, and also that significant losses may occur even in sheep of a moderately susceptible genotype. Similar patterns were not detected in the scrapie-free flocks, indicating that these losses are associated with scrapie infection as well as genotype.

Age Factors↗
PubMed1999

Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie.

The scrapie-associated prion protein (PrPSc), which is closely associated with scrapie infectivity, accumulates in the brain and lymphoid tissues of sheep with natural scrapie. The most probable portal of entry of the scrapie agent in sheep is the alimentary tract; little attention, however, has been paid to the gastro-intestinal tract in scrapie research. In this study, we examined the presence and distribution of PrPSc within the gastro-intestinal tract of sheep with natural scrapie and scrapie-negative sheep. It was found that PrPSc accumulated in the enteric nervous system (ENS) of all scrapie-infected sheep but not in scrapie-negative sheep. The distribution of PrPSc within the ENS was then studied along the entire gastro-intestinal tract in seven scrapie-infected sheep carrying various PrP genotypes. In sheep with the highest genetically determined susceptibility to scrapie, PrPSc was detected in the ENS from the oesophagus to the rectum. In sheep with a lower genetic susceptibility to scrapie, PrPSc was present in the ENS of the forestomachs, small intestine and large intestine but not in the oesophagus. In a scrapie-negative sheep with a PrP genotype associated with scrapie resistance, no PrPSc was seen in the ENS at any site along the gastro-intestinal tract. The presence of PrPSc within the ENS of scrapie-infected sheep indicates a possible role of the ENS in the pathogenesis of natural scrapie as a portal of entry to the central nervous system.

Animals↗
PubMed2002

Differentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strains (CH1641 and SSBP1), bovine spongiform encephalopathy (BSE) cases and Romney and Cheviot breed sheep experimentally inoculated with BSE using two monoclonal antibodies.

A panel of ruminant brain tissues were subjected to a Western immunoblotting technique using two monoclonal antibodies (mAbs). The resultant prion protein (PrP) glycoforms showed that three distinctions can be made between natural ovine scrapie cases and sheep experimentally inoculated with bovine spongiform encephalopathy (BSE). Differentiation between BSE-infected cattle and natural cases of sheep scrapie was also possible using these two antibodies. There were subtle differences in the molecular weight positions of the di-glycosylated, mono-glycosylated and unglycosylated forms of the abnormal PrP (PrP(Sc)) associated with these ruminant transmissible spongiform encephalopathies. In particular, a distinct difference for the unglycosylated protein band was observed. For ovine scrapie samples, this band was noticeably of a higher molecular weight than that found for brain samples from the Romney and Cheviot breed sheep infected with BSE and, to a lesser degree, higher than that observed for bovine BSE samples. Using the comparison of glycoform ratios, the technique provided a distinction between the sheep experimentally infected with BSE and natural cases of sheep scrapie but did not provide a distinction between natural cases of bovine BSE and ovine scrapie. The sheep-passaged CH1641 scrapie strain gave molecular weights similar to, but not identical to BSE, and a glycoform ratio similar to ovine scrapie cases. The SSBP1 experimental scrapie strain gave molecular weights that were akin to natural scrapie cases but the glycoform ratio was different to that found for all the other samples. When mAb P4 was substituted for mAb 6H4 in the technique, only the natural scrapie samples and SSBP1 gave strong signals. BSE in sheep and the CH1641 strain gave weak reactions and PrP(Sc) from BSE-infected cattle could not be detected at all. The results suggest that this combination of molecular weight and glycoform ratio analyses, and differentiation with two specific antibodies could be used to provide a possible screening test for BSE in the UK sheep flock, if confirmed as accurate by bioassay and lesion profile analysis in mice inoculated with brain tissue from suspect field cases.

Animals↗
PubMed1991

Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in British sheep.

We have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and the incidence of natural scrapie in British sheep during the period from July 1988 to November 1990. Sixty percent of the scrapie-positive animals studied were homozygous for a 6.8 kb EcoRI fragment (e1) and a further 26% carried e1 as heterozygotes. This fragment is linked to susceptibility to experimental scrapie in a closed flock of Cheviot sheep. Twelve percent of cases were found to be homozygous for a 4.4 kb EcoRI fragment (e3) which in the Cheviot flock had been linked to relative resistance to scrapie. A third EcoRI fragment of 5.2 kb (e2) has also been found but is relatively rare and has not yet been associated with scrapie susceptibility. Four sets of flocks affected by natural outbreaks of scrapie divided into two groups. In three of these flocks, all scrapie cases carried e1 with high frequencies of e1e1 homozygotes. In the fourth, there were no e1e1 scrapie cases; all scrapie sheep carried e3 in approximately equal numbers of heterozygotes and homozygotes.

Animals↗
PubMed1989

Introduction to scrapie and perspectives on current scrapie research.

Scrapie is the prototype of a family of six transmissible diseases which includes Creutzfeldt-Jakob disease, the only known transmissible human dementia. Bovine spongiform encephalopathy is the most recent addition to the family. Alzheimer's disease is not known to be transmissible. However the pathogenesis of both scrapie and Alzheimer's disease is associated with the modification of (different) normal brain proteins to form various types of amyloid. In scrapie, the evidence suggests that a membrane glycoprotein, PrP, is the precursor of the scrapie associated fibrils (SAF) found in brain extracts, and also of the extracellular deposits of cerebral amyloid which resemble the Alzheimer plaque cores. The host gene that makes PrP is closely linked to the gene Sinc which controls the incubation period of the many different scrapie strains in mice. It is possible that these two genes are the same, i.e., that PrP is the product of Sinc gene. In addition, scrapie infectivity copurifies with modified PrP (SAF). Modified PrP may be the protective protein coat of the independent scrapie genome which some think is a very small nucleic acid. Others believe that the amyloidogenic form of PrP is itself the infectious scrapie agent. Whatever the true situation, there appear to be very short pathways between scrapie infection and amyloidogenesis.

Animals↗
PubMed1990

Scrapie-associated precursor proteins: antigenic relationship between species and immunocytochemical localization in normal, scrapie, and Creutzfeldt-Jakob disease brains.

We describe the antigenic properties and detection of a normal isoform of scrapie-associated precursor protein (PrP33-35C) in normal, and both normal and scrapie isoforms in scrapie- or Creutzfeldt-Jakob disease (CJD)-infected mouse, hamster, and human brains, using a variety of specific antibodies. Polyclonal antibodies raised against mouse and hamster PrP27-30 and against a synthetic peptide of the N-terminal sequence of this protein were used as immunologic probes. PrP27-30 purified as a primary immunogen corresponded to the lower molecular mass peptide, with Mr between 9.3 and 13.5 kd as estimated by size-exclusion high-pressure liquid chromatography. ELISA and immunoblot techniques demonstrated that antibodies recognized homologous antigens as well as precursor proteins from brains (PrP33-35C) and the scrapie isoform of scrapie-associated proteins (PrP33-35Sc/CJD and PrP27-30) from scrapie- and CJD-infected brains. The normal, scrapie, and CJD isoforms of scrapie-associated proteins share common epitopes with varying degrees of interspecies homology. Specific antigen detected in neurons indicated that these proteins are synthesized primarily in these cells. In infected brains, extracellular amyloid deposits formed by the scrapie isoform of PrP protein also strongly reacted with anti-PrP antibodies.

Animals↗
PubMed2006

Scrapie infection activates the replication of ecotropic, xenotropic, and polytropic murine leukemia virus (MuLV) in brains and spinal cords of senescence-accelerated mice: implication of MuLV in progression of scrapie pathogenesis.

Senescence-accelerated mice (SAMP8) have a short life span, whereas SAMR1 mice are resistant to accelerated senescence. Previously it has been reported that the Akv strain of ecotropic murine leukemia virus (E-MuLV) was detected in brains of SAMP8 mice but not in brains of SAMR1 mice. In order to determine the change of MuLV levels following scrapie infection, we analyzed the E-MuLV titer and the RNA expression levels of E-MuLV, xenotropic MuLV, and polytropic MuLV in brains and spinal cords of scrapie-infected SAM mice. The expression levels of the 3 types of MuLV were increased in scrapie-infected mice compared to control mice; E-MuLV expression was detected in infected SAMR1 mice, but only in the terminal stage of scrapie disease. We also examined incubation periods and the levels of PrPSc in scrapie-infected SAMR1 (sR1) and SAMP8 (sP8) mice. We confirmed that the incubation period was shorter in sP8 (210+/-5 days) compared to sR1 (235+/-10 days) after intraperitoneal injection. The levels of PrPSc in sP8 were significantly greater than sR1 at 210+/-5 days, but levels of PrPSc at the terminal stage of scrapie in both SAM strains were virtually identical. These results show the activation of MuLV expression by scrapie infection and suggest acceleration of the progression of scrapie pathogenesis by MuLV.

Animals↗
PubMedDate not supplied

Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie-associated fibrils (SAF).

Brain sections from 16 different mouse scrapie models were immunostained with antisera to scrapie-associated fibrils (SAF) from three experimental scrapie sources (hamster 263K, mouse ME7 and mouse 22L). These models involved seven strains of scrapie injected intracerebrally or intraperitoneally into a range of inbred mouse strains, producing a wide variety of neuropathological changes. The only brain structures which were positively immunostained were amyloid plaque cores in those models in which plaques could be readily identified using traditional amyloid stains. The intensity of immunostaining correlated with the density of amyloid in the cores, as detected by Congo red and thioflavine S staining. No differences in immunostaining specificity were found between antisera or between plaques in different combinations of scrapie strain and mouse genotype. There were also no differences in immunoreactivity between plaques in different parts of the brain. These results strongly suggest that SAF and histologically detectable amyloid in scrapie mice are derived from the same precursor protein. Scrapie-associated cerebrovascular amyloid and plaques in sheep and goats also gave positive immunostaining with SAF antisera, although the lesions in the natural disease could only be stained after formic acid pretreatment. Senile plaques in Alzheimer's disease and Down's syndrome, although structurally similar to scrapie amyloid plaques, were found to be completely negative for SAF, in agreement with previous biochemical and immunocytochemical findings.

Amyloid↗
PubMed2005

Diagnosis and PrP genotype target of scrapie in clinically healthy sheep of Massese breed in the framework of a scrapie eradication programme.

The application of a selective culling programme in two scrapie affected flocks of Massese breed sheep is described. The genetic susceptibility of this breed and the sensitivity of different diagnostic methods in the pre-clinical diagnosis of scrapie were also investigated. Overall, 2,068 clinically healthy sheep underwent PrP genotyping, providing the basis for selective culling. The prevalence of scrapie infection was investigated in susceptible sheep by two independent diagnostic methods. All the sheep older than 18 months (n = 620) were tested by Prionics Check Western rapid test on the obex, with a prevalence of infection of 3.9%. Furthermore, 385 sheep underwent immunohistochemistry (IHC) on retropharyngeal lymph node (RPLN), with a prevalence of infection of 5.2%. Overall, 32 sheep were diagnosed with pre-clinical scrapie. Of these, 31 were positive by Western blot on the spleen, 29 by IHC on the RPLN and tonsil, 28 by IHC on the obex, 24 by rapid test, and only 18 by IHC on the third eyelid. All the scrapie positive sheep were of the ARQ/ARQ, ARQ/AHQ or ARQ/VRQ genotypes. No significant differences in scrapie prevalence were observed among these genotypes. The estimated risk of the three targeted alleles was also similar, suggesting that in this breed the VRQ allele was not at higher risk for scrapie, compared to the ARQ and AHQ alleles.

Alleles↗
PubMed1989

Isolation and purification of scrapie-associated fibrils and prion protein from scrapie-infected hamster brain.

We report the purification of prion protein (PrP) 27-30 and scrapie-associated fibrils (SAF) from hamsters infected with the 263K strain of scrapie. SDS-PAGE of fractions purified from scrapie-infected brains revealed several bands at approximately 28.5 kDa, 23.9 kDa and 14.3 kDa and, in one set of preparations, a protein of Mr 26 kDa was found in both scrapie-infected and sham-inoculated animals. The specificity of PrPs was confirmed by Western blotting. Ultrastructural analysis of fractions from scrapie-infected brains revealed numerous fibrils measuring approximately 20 nm in diameter and 100 to 200 nm in length. The substructure of these fibrils consisted of protofilaments which were usually straight and rarely helically arranged. We conclude that the electron microscopical appearance of SAF depends much on the purification scheme. The PrP27-30 as well as proteins of lower Mr are easily detectable in scrapie-infected brains. The detection of protein of a Mr 26 kDa in both scrapie-infected and sham-inoculated animals suggests that this form of PrP may exist in equilibrium with PrP33-35c.

Animals↗
PubMed2000

Comparison of French natural scrapie isolates with bovine spongiform encephalopathy and experimental scrapie infected sheep.

We compared the glycoform pattern of the abnormal prion protein (PrP(Sc)) detected by immunoblotting in 21 sheep with natural scrapie, from 21 different outbreaks identified in France since 1996, with a bovine spongiform encephalopathy (BSE)-infected sheep. All the natural scrapie isolates had a higher molecular mass of the unglycosylated PrP(Sc) than in BSE-infected sheep. In the latter case, this molecular mass appeared identical to that found in the CH 1641 experimental scrapie strain (type C pattern), whereas in natural scrapie cases it was similar to that found in the SSBP/1 experimental scrapie strains. These results suggest that all French natural scrapie isolates studied so far would belong, as SSBP/1, to the group of scrapie cases with type A electrophoretic pattern.

Animals↗
PubMed1986

Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains.

Scrapie-associated fibrils (SAFs) are abnormal filamentous structures that are uniquely associated with unconventional slow virus diseases. The antigenic relationships of SAFs from animals infected with four biologically distinct scrapie strains were investigated by using antisera raised to purified SAF proteins. Rabbit antisera were raised to SAFs isolated from mice infected with the ME7 scrapie strain and to SAFs isolated from hamsters infected with the 263K scrapie strain. A strong antigenic relationship was shown among SAF proteins (PrPs) isolated from all scrapie-infected animals (ME7, 139A, and 87V in mice and 263K in hamsters), and this relationship was demonstrable regardless of which antiserum was used. SAF proteins were antigenically distinct from those of paired helical filaments or amyloid isolated from patients with Alzheimer disease. Distinct Western blot profiles were demonstrated for SAFs isolated from animals infected with each scrapie strain. Differences seen among SAFs were independent, at least in part, of host species or genotype, implying that certain specific structural and molecular properties of SAFs are mediated by the strain of scrapie agent.

Alzheimer Disease↗
PubMed2006

Derivation of a scrapie-free sheep flock from the progeny of a flock affected by scrapie.

The Cheviot flock at the Institute for Animal Health's Neuropathogenesis Unit (npu) has endemic scrapie, which affects primarily vrq/vrq sheep and at high frequency. A new flock with a full range of PrP genotypes, including the highly susceptible vrq/vrq, has been produced on a separate site, from animals in the npu breeding flock, and it remains scrapie-free after eight years. In contrast, in a parallel flock at the npu farm, scrapie has reappeared after five years, although the animals were kept in separate accommodation from the scrapie-affected sheep. During this time the npu breeding flock continued to have scrapie cases. Although it is known that highly susceptible sheep can remain free of infection in a clean environment, this is the first report of the infection being removed successfully from the bloodlines of scrapie-affected sheep. The results confirm that scrapie is not a genetic disease dependent only on the PrP gene sequence, but requires both genetic susceptibility and an infectious agent.

Animal Husbandry↗
PubMed2002

Search for healthy carriers of scrapie: an assessment of subclinical infection of sheep in an Icelandic scrapie flock by three diagnostic methods and correlation with PrP genotypes.

Subclinical infection in scrapie of sheep, characterized by a long incubation period, may be of importance for the spread of the disease. We screened brain samples from all 65 sheep in a scrapie-affected flock for subclinical infection and correlated with results of PrP genotyping, which is of relevance for the epidemiology and the question, whether by breeding for resistant genotypes one would be breeding for healthy carriers. The sensitivity of three methods was compared, i.e. histopathological examination for vacuoles (HP), immunohistochemical staining (IHC) and Western blotting (WB) for PrP(Sc). Five sheep showed definite clinical signs and histological scrapie lesions, and signs of infection were detected in 25 of 60 asymptomatic sheep, by HP and/or IHC and WB. The IHC was slightly more sensitive than HP and WB. Sheep with subclinical infection were, with one exception, either homo- or heterozygotes for 136-V, as were four of the five sheep with clinical scrapie. The incidence of the VRQ allelic variant in the flock was unusually high compared to the Icelandic sheep population probably contributing to the high prevalence of both clinical and subclinical infection in the flock. Neither sheep with definite scrapie nor detectable subclinical infection, were of the resistant AHQ genotype, indicating that Icelandic AHQ sheep are not healthy carriers of scrapie infection.

Age Factors↗
PubMed2005

The Shetland Islands scrapie monitoring and control programme: analysis of the clinical data collected from 772 scrapie suspects 1985-1997.

There were 574 scrapie positive suspects (histopathological scrapie lesions present) and 198 scrapie negative suspects (histopathological scrapie lesions absent). The greatest number of scrapie cases were recorded in sheep of 2, 3 and 4 years of age which represented 17%, 36% and 23% of the scrapie positive suspects, respectively. The sign sensitivities and specificities for the ten recorded signs were, respectively: pruritus (62%, 42%), ataxia (23%, 74%), hyperaesthesia (32%, 74%), wool loss (25%, 73%), fleece discolouration (29%, 85%), bruxism (23%, 69%), nibbling reflex (17%, 58%), head rubbing (47%, 78%), poll rubbing (25%, 83%). These single signs had poor discriminatory values with likelihood ratios close to one (range 0.89-1.21); combinations of the four signs, pruritus, wool loss, ataxia, hyperaesthesia and emaciation were more discriminatory (range 0.30-4.3). This study covered a time period when bovine spongiform encephalopathy (BSE) might have been introduced into the sheep population on the Shetland Islands via contaminated feed. No temporal changes could be detected in the age structure of the affected animals.

Aging↗
PubMed1991

Scrapie-associated prion protein accumulates in astrocytes during scrapie infection.

In the course of scrapie, a transmissible spongiform encephalopathy caused by an unconventional agent, a normal cellular protein is converted to an abnormal form that copurifies with infectivity and aggregates to form deposits of amyloid. We have used immunocytochemistry and methods that enhance detection of amyloidogenic proteins to investigate the types of cells in the central nervous system which are involved in the formation of the abnormal scrapie-associated protein. We show that this protein accumulates in astrocytes prior to the cardinal neuropathological changes in scrapie--astrogliosis, vacuolation, neuron loss, and amyloid deposition. These findings implicate the astrocyte in the formation of the scrapie isoform of the prion protein and amyloid in scrapie and suggest that this cell type might also be involved in the replication of the scrapie agent.

Amyloid↗
PubMed1998

Scrapie-free Merino and Poll Dorset sheep from Australia and New Zealand have normal frequencies of scrapie-susceptible PrP genotypes.

As natural scrapie occurs only in sheep of specific PrP genotypes, one proposed aetiology was that scrapie is simply a genetic disease. However, Cheviot and Suffolk sheep of scrapie-susceptible genotypes are found in Australia and New Zealand, both generally accepted to be scrapie-free countries. A study of more common Australia and New Zealand sheep breeds (Merinos and Poll Dorsets) was carried out in order to obtain more generally applicable estimates of Australia and New Zealand sheep PrP genotype frequencies. We have confirmed that animals of highly susceptible PrP genotypes are found in Australia and New Zealand. Interestingly, the Poll Dorset sheep, although born in New Zealand, were brought to the UK as young adult animals and subsequently remained free of clinical scrapie despite 21% of the sheep having scrapie-susceptible genotypes. These results have implications for the genetic control of occurrence of the equivalent human diseases.

Age Factors↗