Prion protein gene sequence of Canada's first non-imported case of bovine spongiform encephalopathy (BSE)

Genome ◽  
2003 ◽  
Vol 46 (6) ◽  
pp. 1005-1009 ◽  
Author(s):  
Michael B Coulthart ◽  
Rhonda Mogk ◽  
Jason M Rancourt ◽  
Deborah L Godal ◽  
Stefanie Czub
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Sequence Data ◽  
Spongiform Encephalopathy ◽  
Protein Coding ◽  
Dna Sequence Data ◽  
Imported Case ◽  
The United Kingdom ◽  
Jakob Disease

In May 2003, Canada became the 22nd country outside of the United Kingdom to report a case of bovine spongiform encephalopathy (BSE) in an animal not known to be imported from a country with cattle previously affected by this fatal, transmissible prion disease. Despite extensive testing of thousands of other animals that may have been exposed to contaminated feed at the same time as the affected animal, no evidence has been found for other infections. This finding leaves room for conjectures that the single confirmed case arose spontaneously, perhaps (by analogy with human Creutzfeldt–Jakob disease) as a result of a somatic protein misfolding event or a novel germline mutation. Here we present DNA sequence data from the affected animal's prion protein coding sequence that argue definitively against the latter hypothesis.Key words: bovine spongiform encephalopathy, spontaneous origin, prions, mutation, Canada.

scholarly journals Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein

2012 ◽  
Vol 93 (7) ◽  
pp. 1624-1629 ◽  
Author(s):  
Rona Wilson ◽  
Chris Plinston ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Cristiano Corona ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Human Prion Protein

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

scholarly journals Variant Creutzfeldt-Jakob disease in the United Kingdom

2002 ◽  
Vol 6 (2) ◽  
Author(s):  
F Reid
Keyword(s):  
United Kingdom ◽  
Bovine Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Department Of Health ◽  
The United Kingdom ◽  
Jakob Disease

The Department of Health in the United Kingdom has issued the latest figures on known cases of Creutzfeldt-Jakob disease, including cases of variant Creutzfeldt-Jakob disease (vCJD), the form of the disease linked to bovine spongiform encephalopathy. To 7 January 2002, 104 deaths from vCJD have occurred in the United Kingdom

scholarly journals Variant Creutzfeldt-Jakob disease in the United Kingdom

2002 ◽  
Vol 6 (45) ◽  
Author(s):  
E Hoile
Keyword(s):  
United Kingdom ◽  
Bovine Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Department Of Health ◽  
The United Kingdom ◽  
Jakob Disease

The Department of Health in England has issued the latest figures on known cases of Creutzfeldt-Jakob disease in the United Kingdom (UK), including cases of variant Creutzfeldt-Jakob disease (vCJD), the form of the disease thought to be linked to bovine spongiform encephalopathy.

scholarly journals Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, α-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys

2014 ◽  
Vol 95 (7) ◽  
pp. 1612-1618 ◽  
Author(s):  
Pedro Piccardo ◽  
Juraj Cervenak ◽  
Ming Bu ◽  
Lindsay Miller ◽  
David M. Asher
Keyword(s):  
Neurodegenerative Diseases ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Common Mechanism ◽  
Spongiform Encephalopathy ◽  
Hyperphosphorylated Tau ◽  
Jakob Disease ◽  
Spongiform Degeneration ◽  
Bovine Spongiform Encephalopathy Agent ◽  
Classical Bovine Spongiform Encephalopathy

Proteins aggregate in several slowly progressive neurodegenerative diseases called ‘proteinopathies’. Studies with cell cultures and transgenic mice overexpressing mutated proteins suggested that aggregates of one protein induced misfolding and aggregation of other proteins as well – a possible common mechanism for some neurodegenerative diseases. However, most proteinopathies are ‘sporadic’, without gene mutation or overexpression. Thus, proteinopathies in WT animals genetically close to humans might be informative. Squirrel monkeys infected with the classical bovine spongiform encephalopathy agent developed an encephalopathy resembling variant Creutzfeldt–Jakob disease with accumulations not only of abnormal prion protein (PrPTSE), but also three other proteins: hyperphosphorylated tau (p-tau), α-synuclein and ubiquitin; β-amyloid protein (Aβ) did not accumulate. Severity of brain lesions correlated with spongiform degeneration. No amyloid was detected. These results suggested that PrPTSE enhanced formation of p-tau and aggregation of α-synuclein and ubiquitin, but not Aβ, providing a new experimental model for neurodegenerative diseases associated with complex proteinopathies.

scholarly journals Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

2012 ◽  
Vol 93 (12) ◽  
pp. 2749-2756 ◽  
Author(s):  
Boon Chin Tan ◽  
Anthony R. Alejo Blanco ◽  
E. Fiona Houston ◽  
Paula Stewart ◽  
Wilfred Goldmann ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Prnp Gene ◽  
Brain Homogenate ◽  
Spongiform Encephalopathy ◽  
Direct Effects ◽  
Prion Infection ◽  
Incubation Periods

The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the A136R154Q171 allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was observed in LL141 sheep, whilst incubation periods in FF141 and LF141 sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates.

scholarly journals Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Hideyuki Hara ◽  
Hironori Miyata ◽  
Nandita Rani Das ◽  
Junji Chida ◽  
Tatenobu Yoshimochi ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Jakob Disease ◽  
Function Relationship ◽  
Different Strains ◽  
Conformational Conversion

ABSTRACTConformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPCinto PrPScafter infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/Prnp0/0mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPCinto PrPScafter infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0mice than PrPScin control wild-type mice. Taken together, these results indicate that the OR region of PrPCcould play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.IMPORTANCEStructure-function relationship studies of PrPCconformational conversion into PrPScare worthwhile to understand the mechanism of the conversion of PrPCinto PrPSc. We show here that, by inoculating Tg(PrPΔOR)/Prnp0/0mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrPCinto PrPScafter infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPCinto PrPScafter infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.

scholarly journals Bovine Spongiform Encephalopathy (BSE) in Japan. How was the “Blanket Testing Myth” Created?

2007 ◽  
Vol 2 (2) ◽  
pp. 81-89 ◽  
Author(s):  
Hideaki Karaki ◽  
Keyword(s):  
Risk Communication ◽  
Bovine Spongiform Encephalopathy ◽  
Clinical Symptoms ◽  
Spongiform Encephalopathy ◽  
The United Kingdom ◽  
Long Time ◽  
Jakob Disease ◽  
Uk Government ◽  
The Government ◽  
The Uk

In 1986, after bovine spongiform encephalopathy (BSE) was discovered in the United Kingdom, over 183,000 cases have been confirmed to date. In 1996, the UK government announced that BSE may be transmitted to humans, causing variant Creutzfeldt-Jakob disease (vCJD). Retrospectively, the measures taken by the UK government were appropriate and the number of new cases of both BSE and vCJD decreased. Because of the long incubation period between infection and the appearance of clinical symptoms in both BSE and vCJD, a long time was needed to determine the effects of these measures. The inappropriate risk communication, however, caused people to lose trust in the UK government, and fear spread. In Japan, a cow infected with BSE was found in 2001. Although no cattle showing BSE symptoms were found and the risk of BSE infection was low, fear again spread due to inadequate risk communication. To allay consumer anxieties, the government began testing all cattle at slaughter facilities. This, in turn, generated the "blanket testing myth" - the misunderstanding that BSE testing was the most important measure needed to maintain the safety of beef consumption.

scholarly journals A field on fire: The biochemistry of mad cows

2005 ◽  
Vol 27 (4) ◽  
pp. 6-8
Author(s):  
David R. Brown
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Spongiform Encephalopathy ◽  
Related Disease ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.

scholarly journals Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions

2016 ◽  
Vol 90 (21) ◽  
pp. 9558-9569 ◽  
Author(s):  
Joel C. Watts ◽  
Kurt Giles ◽  
Daniel J. Saltzberg ◽  
Brittany N. Dugger ◽  
Smita Patel ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Guinea Pigs ◽  
Spongiform Encephalopathy ◽  
Prolonged Incubation ◽  
Rapid Propagation ◽  
Incubation Periods ◽  
Jakob Disease ◽  
Sporadic Cjd

ABSTRACTThe biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrPSc, were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates.IMPORTANCEVariant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for propagating BSE and vCJD prions.

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