Clinical and pathological changes in familial Creutzfeldt-Jakob disease (CJD) cases may be similar or indistinguishable from sporadic CJD. Therefore determination of novel mutations in PRNP remains of major importance. We identified two different rare mutations in codon 188 of the prion protein gene (PRNP) in four patients suffering from a disease clinically very similar to the major subtype of...

Susceptibility to scrapie is primarily controlled by polymorphisms in the ovine prion protein gene (PRNP). Here, we report a novel ovine exon three PRNP polymorphism (SNP G346C; P116), its association with the ovine ARQ allele (P116A136R154Q171), and two new genotypes (PARQ/ARR; PARQ/ARQ) for the St. Croix White (SCW) breed and a related composite (CMP) breed developed for meat production. The ...

PrP knockout mice in which only the open reading frame was disrupted ('Zürich I') remained healthy. However, more extensive deletions resulted in ataxia, Purkinje cell loss and ectopic expression in brain of Doppel (Dpl), encoded by the downstream gene, PRND: A new PrP knockout line, 'Zürich II', with a 2.9 kb PRNP: deletion, developed this phenotype at approximately 10 months (50% morbidity). ...

Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother ...

Using PrPC-knockout cell lines, it has been shown that the inhibition of apoptosis through STI1 is mediated by PrPC-dependent SOD activation. Antioxidant PrPC may contribute to suppression of inflammasome activation. PrPC is functionally involved in copper metabolism, signal transduction, neuroprotection, and cell maturation. Recently several reports have shown that PrPC participates in trans-m...

The aims of the study were to detect the polymorphisms of three microsatellite sites: S11, S15, and S24 in the ovine PRNP and to asses their relationship with prion protein (PrP) genotypes in three sheep breeds. To identify 15 PrP genotypes based on polymorphisms at codons 136, 154, and 171, PCR-RFLP analyses were applied. The microsatellite sites were amplified. For each microsatellite two or ...

This report describes the genetics of the prion protein gene (PRNP) at codons 136, 154, and 171 for sheep diagnosed with naturally acquired classical scrapie in Canada between 1998 and 2008. Genotyping analysis was performed on 249 sheep with confirmed classical scrapie infection representing 98 flocks from 6 provinces. A further case-control analysis of 3 of these flocks compared the genotypes...

Brucella abortus is a Gram-negative bacterium causing brucellosis. Although B. abortus is known to infect via the oral route, the entry site in the gastrointestinal tract has been unclear. We found that B. abortus was selectively internalized by microfold cells (M cells), a subset of epithelial cells specialized for mucosal Ag uptake. During this process, colocalization of cellular prion protei...

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of rare and fatal neurodegenerative disorders that affect both humans and animals. The etiology of TSEs contributed to the important “protein-only” hypothesis, which postulates that proteinaceous particles known as “prions, which are devoid of nucleic acids, are the causative agents of TSEs. Human TSEs a...

The Prnp gene encodes the cellular prion protein PrP(C). Removal of its ORF does not result in pathological phenotypes, but deletions extending into the upstream intron result in cerebellar degeneration, possibly because of ectopic cis-activation of the Prnd locus that encodes the PrP(C) homologue Doppel (Dpl). To test this hypothesis, we removed Prnd from Prnp(o/o) mice by transallelic meiotic...