Proteinase-activated receptor 2 (PAR2) is suspected to modulate the pathogenesis of various neurodegenerative conditions. We previously described delayed onset of clinical symptoms and prolonged survival of PAR2-deficient mice after intracerebral inoculation with prions. Here we report the results from a refined blinded study that aimed to investigate the effects of PAR2 deletion on scrapie pathogenesis after peripheral infection. This study failed to confirm that PAR2 deficiency impacts on the length of the incubation period, with PAR2-/- and PAR2+/+ littermates developing scrapie at the same time. To clarify the discrepancy between the two observations, we repeated the intracerebral inoculation study while utilizing our refined protocol, which aimed to limit possible sources of experimental bias. The study again failed to confirm the significant effect of PAR2 expression on the course of prion infection. Our report emphasizes and discusses the importance of unbiased experimental design and the selection of proper genetic controls when using genetically altered animal models for prion pathogenesis studies.

• MeSH
• Disease Models, Animal MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Receptor, PAR-2 deficiency   metabolism   MeSH
• Scrapie physiopathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Of 34 breeds kept in the Czech Republic 45,604 sheep were genotyped for codons 136, 154 and 171 in the prion protein gene (PRNP) during the years 2006-2014. In this cohort, haplotypes ARR, ARQ, ARH, AHQ, VRQ, AHR and ARK were detected. The haplotype AF141RQ associated with susceptibility to atypical scrapie was observed in nine out of 30 breeds analysed for this purpose. In addition, six rare nonsynonymous substitutions producing haplotypes AT137RQ, AN138RQ, AG151RQ, AH151RQ, ARL168Q and ARQE175 were identified in various breeds. Due to their low frequencies, these polymorphisms are of no potential importance for the breeding programme. With regard to their genetic particularity, Sumavka, Valachian and Cameroon breeds were screened for additional polymorphisms. Further haplotypes, AR143RQ and AS146RQ, were found in Sumavka and Cameroon, and in Valachian sheep, respectively. Frequencies of the ARR (resistance-associated), VRQ (susceptibility-associated) haplotypes, and of the most resistant ARR/ARR genotype calculated for sheep born in the years 2001-2003 and 2011-2013 documented effects of the 10 year-lasting national breeding programme. The total frequency of ARR doubled from 36.8 to 75.8 %, while the frequency of VRQ decreased from 4 to 0.7 %. The total frequency of the ARR/ARR genotype increased from 17.7 to 59 %. These data show that the national scrapie resistance breeding programme has had an important desirable effect on haplotype and genotype frequencies of PRNP in Czech sheep.

• MeSH
• Breeding MeSH
• Gene Frequency MeSH
• Genetic Predisposition to Disease * MeSH
• Genotype MeSH
• Haplotypes MeSH
• Sheep, Domestic genetics   MeSH
• Polymorphism, Genetic MeSH
• Prion Proteins genetics   MeSH
• Scrapie genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Creutzfeldt-Jakob Syndrome diagnosis   epidemiology   etiology   pathology   veterinary   MeSH
• Kuru etiology   MeSH
• Humans MeSH
• Prions analysis   history   adverse effects   MeSH
• Scrapie diagnosis   epidemiology   transmission   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Historical Article MeSH
• Geographicals
• New Guinea MeSH

Proteinase-activated receptor 2 (PAR2) has recently been identified to be a possible modulator of neurodegeneration. To investigate whether PAR2 plays a role in prion infection, we inoculated PAR2-deficient (PAR2(-/-)) and wild-type (WT) mice intracerebrally with the Rocky Mountain Laboratory strain of scrapie. PAR2(-/-) mice demonstrated a delayed onset of clinical symptoms, including weight loss, and demonstrated moderate but highly significant prolongation of survival over WT controls. Concomitantly, no apparent differences in brain pathology, infectivity or features of brain prion protein between deceased WT and PAR2(-/-) mice were found. Our study suggests that PAR2 deletion modulates dynamics of the disease without gross perturbation of its pathogenesis.

• MeSH
• Gene Deletion MeSH
• Humans MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Prions genetics   metabolism   MeSH
• Receptor, PAR-2 deficiency   genetics   MeSH
• Scrapie enzymology   genetics   metabolism   mortality   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Problematika prionových neuroinfekcí se stala velmi naléhavou záležitostí po vzniku epidemie bovinní spongiformní encefalopatie, která kulminovala v roce 1993. Jednotlivé případy se stále vyskytují. Dalším důvodem byl objev nové varianty Creutzfeldt-Jakobovy nemoci u relativně mladších osob, u kterých byla prokázána souvislost s alimentární cestou nákazy, dosud bylo popsáno asi 140 postižených. Fyziologické priony jsou glykoproteiny, zakotvené v raftech celulárních membrán (zejména neuronů) glykosylfosfatidylinositolovou kotvou. Působí jako signalizační molekuly a účastní se na metabolizmu mědi. Intenzivní výzkum řady renomovaných laboratoří dosud neprokázal s jistotou, jakým způsobem vzniká patogenní izoforma prionů, daná převahou beta-konformace v polypeptidovém řetězci. Patogenní izoformy se tvoří intracelulárně po předchozí endocytóze. Agregací abnormálních prionových molekul vznikají prionová amyloidní depozita v podobě fibril a plátů, uložených v neuropilu. Neurologickou symptomatologii vyvolává zánik neuronů, který není zcela úměrný množství amyloidních depozit. Charakteristický nález spongiózy a imunohistochemický průkaz k proteázám rezistentního prionu jsou jedinými spolehlivými testy. Spolehlivý intravitální test z krve či moči zatím není k dispozici. Všechny druhy lidských i zvířecích transmisivních spongiformních encefalopatií vznikají jen u geneticky vnímavých jedinců. Je podán stručný přehled klinických forem a některých aspektů z oboru biochemie a genetiky.

Prion neuroinfections represent an emergent problem namely after the epidemic brake out of the bovine spongiform encephalopathies, which culminated in 1993. Isolated cases can still emerge. The next case was the discovery of a new variant of Creutzfeldt-Jakob disease in the comparatively young persons with proved alimentary infection route – about 140 cases has been described. Physiological prions are glycoproteins, affixed to the rafts of cell membranes (namely in neurons) by glycosylphosphatidylinositol anchor. They act as signalling molecules and participate in the cooper metabolism. Despite the intensive study in many prestigious laboratories, the way how the pathogenicis oform of prions, given by the prevalence of beta-conformations in the polypeptide chain develops has not been proved yet. Pathogenic isoforms are formed intracellulary after the precedent endocytosis. Aggregations of abnormal prion molecules build up prion amyloid deposits in the form of fibrils or plaques. The loss of neurons brings about the neurological symptoms, which are not directly related to the amounts of amyloid deposits. Characteristic findings of spongiosis and the immunohistochemical evidence of protease-resistant prions belong to the only reliable tests. Reliable intravital test in the blood or urine is not yet available. All forms of human and animal transmissible spongiform encephalopathies develop only in genetically sensitive individuals. A brief overview of clinical forms and some biochemical and genetic aspects of the disease are given.

• MeSH
• Creutzfeldt-Jakob Syndrome diagnosis   transmission   therapy   MeSH
• Slow Virus Diseases transmission   MeSH
• Humans MeSH
• Prion Diseases diagnosis   transmission   therapy   MeSH
• Prions pathogenicity   MeSH
• Scrapie pathogenicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Prion Diseases genetics   immunology   MeSH
• Scrapie diagnosis   immunology   transmission   MeSH
• Zoonoses transmission   MeSH
• Publication type
• Congress MeSH
• Geographicals
• Slovakia MeSH

• MeSH
• Genotype MeSH
• Sheep MeSH
• Prions analysis   genetics   MeSH
• Scrapie genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

• MeSH
• Enzyme-Linked Immunosorbent Assay utilization   MeSH
• Encephalopathy, Bovine Spongiform pathology   MeSH
• Scrapie diagnosis   pathology   MeSH
• Blotting, Western utilization   MeSH
• Publication type
• Review MeSH

• MeSH
• Creutzfeldt-Jakob Syndrome epidemiology   MeSH
• Humans MeSH
• Models, Animal MeSH
• Prion Diseases etiology   transmission   MeSH
• Prions physiology   genetics   chemistry   MeSH
• Scrapie etiology   transmission   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH

Kniha podrobně líčí přenos záhadné nemoci ovcí, známé již v 18. století na hovězí dobytek. Epidemie této nemoci se rozhořela v Británii od roku 1975. Práce popisuje původ BSE a podmínky přenostnosti na skot i na lidi v dalších zemích a od 80. let 20. století. Závěrečné kapitoly přinášejí přehled lidských obětí nemoci šílených krav a seznamují s metodami prevence této zhoubné nemoci. Monografie je provázena grafy v textu a doplněna podrobným přehledem použité literatury a věcným rejstříkem.

• MeSH
• Creutzfeldt-Jakob Syndrome history   epidemiology   transmission   MeSH
• Encephalopathy, Bovine Spongiform epidemiology   prevention & control   transmission   MeSH
• Epidemics MeSH
• Kuru history   epidemiology   transmission   MeSH
• Prion Diseases epidemiology   prevention & control   transmission   MeSH
• Scrapie history   epidemiology   transmission   MeSH
• Publication type
• Popular Work MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• infekční lékařství
• epidemiologie