The utility of bank voles for studying prion disease

Arshad, Hamza; Bourkas, Matthew E.C.; Watts, Joel C.

doi:10.1016/bs.pmbts.2020.08.009

Cited by 12 publications

(8 citation statements)

References 127 publications

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“…It has been also used to assess the zoonotic potential of animal prion diseases such as BSE, scrapie, CWD, and atypical prion diseases. For instance, studies have confirmed that PMCA exhibits species specificity that faithfully reflects the same transmission barrier observed in animals in vivo [ 1 , 10 , 16 , 28 ]. When BSE and scrapie were examined for their capability to convert human PrP with the three major polymorphic variants ( PRNP codon 129 MM, MV and VV) expressed in the humanized transgenic mouse brain [ 5 , 17 ], cattle BSE prions was able to trigger the efficient conversion of human PrP with a preference similar to that of human vCJD (MM > MV > VV) while scrapie failed to convert the human substrates [ 17 ].…”

Section: Discussionmentioning

confidence: 96%

Generation of human chronic wasting disease in transgenic mice

Wang

Qin

Camacho

et al. 2021

acta neuropathol commun

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Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

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Section: Discussionmentioning

confidence: 96%

Generation of human chronic wasting disease in transgenic mice

Wang

Qin

Camacho

et al. 2021

acta neuropathol commun

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“…Proteins were then dissolved in the sample buffer (3% SDS, 3% β-mercaptoethanol, 2 mM EDTA, 10% glycerol, 62.5 mM Tris, pH 6.8, Merck) and boiled for 5 min. An equivalent of 0.4 mg of wet tissue was loaded on 13% SDS-PAGE gels, and the proteins were transferred onto PVDF membrane (Immobilon P, Millipore, Merck Life Science, Milano, Italy) for 2 h at 60 V. Membranes were blocked with 1% non-fat dry milk in TBST (10 mM Tris, 150 mM NaCl, 0.1% Tween-20, pH 7.5) for 1 h at 37 °C and incubated overnight at 4 °C with anti-PrP monoclonal antibodies 3F4 and SA21 [ 33 ]. According to the producer, 3F4 (1:5000, Covance, Princeton, NJ, USA, catalog# SIG-39620) recognizes the human PrP sequence between 109 and 112, while our SA21 (1:1000) distinguishes between residues 165 and 185 of both unglycosylated PrP and PrP glycosylated at position 197, but it does not recognize PrP isoforms glycosylated at 181 [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene

Zanusso

Colaizzo

Poleggi

et al. 2022

IJMS

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Genetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

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“…Having established a method that allows to reliably identify all relevant PrP C proteoforms, we next aimed at comparing the endoproteolytic processing of PrP C of bank voles and wild type mice, two rodent models that show different susceptibility to prion diseases (64)(65)(66)(67)(68)(69)(70)(71). We first aimed to confirm antibodies reactivity in mouse brain and found that all antibodies but EP1802Y equally detected vole and mouse PrPs (Suppl.…”

Section: Endoproteolytic Processing Of Prp C In Wild Type Micementioning

confidence: 99%