scrapie

..after various treatments intended to inactivate or remove TSE agents (using the 263K strain of hamster-adapted scrapie agent as a model)...

..Determinations of acetylcholinesterase activity in scrapie inoculated PC12 cell culture have not to date shown a significant difference in activity from those obtained from ..

..TSE) are a group of rare neurodegenerative diseases which include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) in mule deer and elk...

TSEs are a group of neurodegenerative diseases affecting a wide variety of mammals including sheep and goats (scrapie), cervid spp. (chronic wasting disease), and humans (Creutzfeldt-Jakob disease)...

..Oral transmission is the primary route of infection for BSE, scrapie and TME and is the suspected route of transmission for vCJD and CWD...

..agents responsible for fatal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) in cattle...

..in cattle, chronic wasting disease (CWD) in deer and elk, transmissible mink encephalopathy (TME) in mink, and scrapie in sheep. The infectious agents of TSEs are unconventional, proteinaceous entities, which have been termed prions...

DESCRIPTION (provided by applicant): The "protein-only hypothesis" states that prion diseases such as scrapie in sheep, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease in human are distinct from infectious diseases ..

..To investigate the issue of cross-species transmission we used an animal model involving transmission of hamster scrapie agent to mice (prior to our study mice were considered resistant to hamster scrapie)...

..we plan to study three strains of prions passaged in mice: RML and 301V, which originated from sheep with scrapie and cattle with BSE, respectively, plus a novel synthetic strain MoSP1, which is the most stable strain reported ..

..spongiform encephalopathies (TSEs or prion disease), which are fatal neurodegenerative diseases such as scrapie, Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy and chronic wasting disease (CWD)...

..There have been precedents when vaccines accidentally prepared from tissues of scrapie-infected sheep caused scrapie outbreaks involving hundreds of immunized animals...

..or from CWD-affected animals including: Rocky Mountain elk, mule deer, white-tail deer, cattle, and sheep; sheep scrapie will also be inoculated as a control...

..or from CWD-affected animals including: Rocky Mountain elk, mule deer, white-tail deer, cattle, and sheep; sheep scrapie will also be inoculated as a control...

..the same pathogenic mechanism based on the conversion of the normal cellular prion (PrP c) into the infectious scrapie prion (prpSc)...

..TSEs, or prion diseases, include Creutzfeldt-Jakob disease, fatal familial insomnia and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk...

..TSEs, or prion diseases, include Creutzfeldt-Jakob disease, fatal familial insomnia and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk...

..These include chronic wasting disease (CWD) of deer and elk, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jacob disease and kuru in humans...

..encephalopathies (TSE) are degenerative brain diseases that occur in primates and ruminants, and include scrapie in sheep, bovine spongiform encephalopathy (BSE) and several human diseases such as Creutzfeldt-Jakob disease, ..

..is the encephalopathies such as Creuzfeld-Jacob disease in humans, BSC (or 'mad cow disease') in cattle and scrapie in sheep...

..protein accumulation in lymphoid tissues is an intriguing and likely important feature of several TSE including scrapie in sheep, CWD in deer and nvCJD in humans...

..Despite these concerns, surprisingly little is known about the mechanism(s) by which the infectious prion or PrP-scrapie (PrPsc), a protein of 27-30kDa, is transported from the intestine or peripheral blood to the central nervous ..

..The aims of this project are to perfect the Scrapie Cell Assay (SCA), which allows the sensitive and rapid quantification of prions in cell culture rather than by ..

..The aims of this project are to perfect the Scrapie Cell Assay (SCA), which allows the sensitive and rapid quantification of prions in cell culture rather than by ..

..Molecules recovered via both of these strategies will be evaluated for their capacity to resolve prion infection in vitro and in vivo. Public Health Relevance: This Public Health Relevance is not available...

..topical, and important feature of several TSEs, including variant Creutzfeldt-Jakob disease (vCJD) in humans, scrapie in sheep, and chronic wasting disease (CWD) in deer...

..the transmissible spongiform encephalopathies (TSE), which include Creutzfeldt Jakob disease (CJD) in humans and scrapie in sheep, remains an enigma. In this application we present evidence for the association of Spiroplasma sp...

..to animals were obtained with a notable exception of prion diseases such as Creitzfeldt-Jakob disease in man and scrapie and mad cow disease in animals...

..blood, bone marrow purging, and for inhibition of transmissible spongiform encephalopathies [bovine (BSE), sheep (scrapie) and human forms (Creutzfeld-Jacob disease)]...

..after various treatments intended to inactivate or remove TSE agents (using the 263K strain of hamster-adapted scrapie agent as a model)...

..of any human transmissible spongiform encephalopathy (TSE), animals experimentally infected with the agents of scrapie and two variants of Creutzfeldt-Jakob disease (CJD) were consistently found to have infectivity in blood during ..

..clearly demonstrated a disruption in the differentiation and phenotype of these two B cell subsets in response to scrapie infection...

..We have carried out all of the in vivo studies of UPS function in scrapie-inoculated mice using a transgenic mouse line developed by Dr. Dantuma...

..Abstract): Neuronal death in prion disorders is believed to result from a conformationally transformed, scrapie isoform (PrPSc) of the normal host prion protein (PrPC)...

..The goal of this project is to use a comparative transcriptomics approach on scrapie permissive sheep cell lines to identify possible accessory proteins necessary for PrP accumulation...

..prion based on the CANARY biosensor technology developed at MIT and an antibody that specifically recognizes the scrapie form of the prion protein in cattle and humans...

..impact upon human and animal health are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE), scrapie and chronic wasting disease (CWD)...

..impact upon human and animal health are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE), scrapie and chronic wasting disease (CWD)...

..They will be spiked with scrapie and irradiated at several dosages under varying conditions...

..Gerstmann-Straussler-Scheinker diseases (GSS), and fatal familial insomnia (FFI); and five diseases of animals--scrapie, transmissible mink encephalopathy (TME), chronic wasting disease of deer and elk (CWD), feline spongiform ..

..arrays were identified in two different cell types infected with two very different TSE agents (FU-CJD and 22L-scrapie). We propose to develop rapid live cell culture assays of infectivity for these two TSE agents...

..CJD) and variant CJD, Gerstmann- Straussler-Scheinker disease, Fatal Familial Insomnia, and kuru (humans), scrapie (sheep), chronic wasting disease (elk, deer), and mad cow disease (cattle)...

..Even the mechanisms by which alternative alleles of Prnp determine scrapie incubation time are unresolved...

..provided by applicant): In the brains of humans and animals affected by prion disorders such as vCJD, BSE, scrapie, and chronic wasting disease, a cellular glycoprotein termed PrPC converts into an insoluble, pathogenic isoform ..

..During the project period, I expressed mutant PrP genes in scrapie-infected neuroblastoma (ScN2a) cells and transgenic (Tg) mice, and studied the pathological and biochemical ..

..PrPC form and a toxic PrPSc form that causes the Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, scrapie, and other spongiform encephalopathies...

..amplification to measure the potential susceptibility of a range of potential host species to CWD as well as scrapie. Species to be tested include humans, cows, pigs, sheep, goats, chickens, dogs, cats, coyotes, foxes, raccoons, ..

..measurements of fluorescence from untreated and proteinase K (PK)-treated PrP(Sc), purified from 263K scrapie strain-infected hamster brains and ME7 scrapie strain-infected mouse brains, were performed...

..They include scrapie in sheep, bovine spongiform encephalopathy in cattle, as well as Creutzfeld-Jakob disease, Gerstmann-Straussler-..

..we generated mutant anchorless (GPInegative) PrP, and when these molecules were coincubated in vitro with scrapie brain extracts, they were converted to the abnormal scrapie-associated PrPres isoform, characterized by its ..

..well as analysis of potential differences in incubation time/disease incidence among different strains of mouse scrapie. The third tg model is the expression of white tail deer (WTD) prion under control of the mouse PrP promoter in ..

..well as analysis of potential differences in incubation time/disease incidence among different strains of mouse scrapie. The third tg model is the expression of white tail deer (WTD) prion under control of the mouse PrP promoter in ..

..cellular prion protein (PrPC) leading to the accumulation of an abnormal protease-resistant isoform (PrPSc or the scrapie isoform of PrPc)...

..cellular prion protein (PrPC) leading to the accumulation of an abnormal protease-resistant isoform (PrPSc or the scrapie isoform of PrPc)...

..directed at understanding the structure of the transmembrane type of abnormal PrP, CtmPrP, which is found in both scrapie and Gerstmann-Straussler-Scheinker type prion disease...

..brain are involved in protein misfolding and aggregation in two protein-folding diseases: Alzheimer's disease and scrapie. We hypothesize that elevated concentrations of metal ions (notably Cu, Fe, and Zn) in the brain are involved in ..

..That aim was to determine the tissue distribution and titers of infectious deer scrapie inoculated into tg mice that have their murine PrP gene ko and replaced by deer PrP controlled by murine PrP ..

..Animal Core personnel include 1) Production of transgenic and knockout mice, 2) Production of large volumes of scrapie-infected hamsters and mouse brains for purification, 3) Performing experimental inoculations, neurologic scoring ..

..Determinations of acetylcholinesterase activity in scrapie inoculated PC12 cell culture have not to date shown a significant difference in activity from those obtained from ..

..We have discovered comparable viruslike particles in cultures with high titers of scrapie infectivity, and thus we suspect such particles can also aid in the diagnosis, prevention and fundamental ..

The insolubility of the scrapie prion protein (PrPSc) has frustrated all attempts to solve its structure by X-ray crystallography or NMR spectroscopy...

..Animal Core personnel include 1) Production of transgenic and knockout mice, 2) Production of large volumes of scrapie-infected hamsters and mouse brains for purification, 3) Performing experimental inoculations, neurologic scoring ..

Sheep scrapie has been known for at least 200 years and was described as a transmissible disease over 100 years ago...

Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity led to the discovery of the prion protein (PrP)...

..These mice also posed no transmission barrier for Suffolk sheep scrapie prions, suggesting that cattle may be highly susceptible to some sheep scrapie strains...

..Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded...

..These findings suggest a critical role for the structurally 'flexible' region of PrP in agent replication and targeting of TSE pathology...

..can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern...

..and PrP genetics of the transmission of BSE to sheep and goats, with the effects of the transmission of natural scrapie from a brain homogenate from a single sheep...

..Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrP(Sc) ..

..Therefore, infected primary neuronal cultures may be a relevant system in which to investigate the efficacy and mode of action of antiprion drugs, including toward human transmissible spongiform encephalopathy agents...

A procedure for discrimination between scrapie and bovine spongiform encephalopathy (BSE) in sheep is of importance for establishing whether BSE has entered the sheep population...

..The occurrence of atypical cases only in animals 9 years of age and older raises questions about the mechanisms of prion diseases and the origin of BSE...

b>Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ..

..The transmission routes of scrapie and chronic wasting disease (CWD) seem to include environmental spread in their epidemiology, yet the fate of TSE ..

..on primary cerebellar cultures established from transgenic mice expressing ovine PrP and then exposed to sheep scrapie agent...

....

..We hypothesize that both the presence of PrP(Sc) or the absence of PrP(C) may alter the metabolism of GAGs...

..fail to prevent the formation of protease-resistant, misfolded forms of PrP (ScPrP) during the development of scrapie and other transmissible spongiform encephalopathies, and ScPrP is a biochemical marker of these diseases...

Prion diseases are characterized by a long incubation period. In scrapie, sheep may incubate and spread the infection for several years before clinical signs evolve...

The central molecular event in transmissible spongiform encephalopathies, such as scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the cellular prion protein...

..different TSE strains, including differentiation of agents involved in bovine spongiform encephalopathy (BSE) and scrapie, this has been only poorly described in transgenic mice...

..antibodies (MAbs) specific for prion protein (PrP) were generated by using PrP-knockout mice immunized with a scrapie-infected mouse neuroblastoma cell line (N2a/22L)...

..In addition, SY-CJD prevented superinfection by sheep-derived Chandler (Ch) and 22L scrapie agents...

The histological diagnosis of transmissible spongiform encephalopathies (TSEs), such as scrapie and bovine spongiform encephalopathy (BSE), relies on identification in the brain of spongiosis, gliosis, and neuron loss without ..

In the past, natural scrapie and bovine spongiform encephalopathy (BSE) infections have essentially not been diagnosed in sheep homozygous for the A136R154R171 haplotype of the prion protein...

..In this national survey, 186 scrapie-affected sheep were found which originated from 78 flocks...

..Transgenic mice expressing chimeric murine/ovine PrP(C) (Tgmushp mice) are susceptible to BSE and/or scrapie prions of bovine or ovine origin while transgenic mice expressing similar murine/bovine PrP(C) chimera (Tgmubo ..

..Accordingly, mice expressing PrP-Fc(2) but lacking endogenous PrP(C) are resistant to scrapie, do not accumulate PrP-Fc(2)(Sc), and do not transmit disease to others...

b>Scrapie of sheep and goats is the most common prion disease (or transmissible spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase-resistant prion protein (PrP(Sc)) are found in all naturally occurring prion ..

..In addition, it was observed that TSE symptoms and subsequent death of plasminogen-deficient and tPA-deficient scrapie challenged mice preceded that of wild-type controls...

..These data raise the possibility that apically expressed PrP may be involved in this polarized process of infection. This would add further support for a crucial role of PrP at the cell surface in prion infection of target cells...

Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or ..

..The diseases have been well known for decades. Scrapie was first described around 1750, a BSE case was reported in the 1850-ties most likely a misdiagnosis, and in 1920/..

b>Scrapie-infected mice are considered a model for study in prion diseases, which are characterized by the progressive accumulation in the brain of an abnormal isoform (PrPsc) of the normal cellular prion protein (PrPc)...

..These studies are consistent with the view that the proportion of each glycoform incorporated into PrPSc is probably controlled in a strain-specific manner and that each PrPSc particle contains a mixture of glycoforms...

..immunoprecipitation, sphAb3-15 efficiently bound to PrP from normal brain homogenates, but weakly bound PrP from scrapie-infected brain homogenates...

Prion disease is characterized by a conformational change of the normal form of the prion protein (PrP(C)) to the scrapie-associated form (PrP(Sc))...

..RESULTS: A standardized preparation of materials has been generated. CONCLUSIONS: Large-scale preparations of tissues and blood fractions can be used to directly compare the sensitivities of assays using different formats...

OBJECTIVE: Scrapie of sheep and Creutzfeldt-Jakob disease (CJD) are both classified as prion diseases. The infectious agents of both diseases are closely related...

b>Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) or prion diseases affecting domestic and exotic ruminants...

..These features, together with the conventional lesion profile, will be of use in distinguishing the agents of BSE and scrapie in sheep.

b>Scrapie, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease belong to the group of disorders called transmissible spongiform encephalopathies or prion diseases...

Molecular analyses of the protease-resistant prion protein (PrP(res)) from a few natural scrapie isolates showed by Western blotting some partial similarities with those observed in experimental ovine bovine spongiform encephalopathy (..

..group of fatal neurodegenerative disorders represented principally by Creutzfeldt-Jakob disease in humans, and by scrapie and bovine spongiform encephalopathy in animals...

b>Scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep and goats...

The incubation period of scrapie in sheep is controlled by the Sip gene which has two alleles (sA and pA). Following experimental challenge with SSBP/1 scrapie, a short incubation period is conferred by the partially dominant sA allele...

..Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features...

The application of a selective culling programme in two scrapie affected flocks of Massese breed sheep is described...

b>Scrapie diagnosis is based on the demonstration of disease-associated prion protein (PrP(Sc)) in brain or, in the live animal, in readily accessible peripheral lymphoid tissue...

..Using this new technique, the sensitivity to identify samples from scrapie-infected hamster as well as BSE-infected cattle can be dramatically increased in comparison with identification ..

..CONCLUSIONS: There is still no treatment for CJD. Further studies of the physiopathological mechanisms of prion diseases may help in the development of treatment to delay the progress of this disease...