Quantitative Trait Loci Affecting Prion Incubation Time in Mice

Stephenson, Dennis A.; Chiotti, Kami; Ebeling, Christine; Groth, Darlene; DeArmond, Stephen J.; Prusiner, Stanley B.; Carlson, George A.

doi:10.1006/geno.2000.6320

Cited by 117 publications

(93 citation statements)

References 42 publications

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“…Studies using model systems have also suggested that hostencoded factors other than PrP C may be required to propagate prions in vitro and in vivo (5)(6)(7)(8)(9)(10). Furthermore, the restricted range of neuronal and nonneuronal cell types that are susceptible to infection by prions also suggests the existence of prion propagation cofactors (11)(12)(13).…”

mentioning

confidence: 99%

Formation of native prions from minimal components in vitro

Deleault¹,

Harris²,

Rees³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

585

635

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The conformational change of a host protein, PrP C , into a disease-associated isoform, PrP Sc , appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt–Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown. To investigate the mechanism of prion formation biochemically, we conducted a series of experiments using the protein misfolding cyclic amplification (PMCA) technique with a preparation containing only native PrP C and copurified lipid molecules. These experiments showed that successful PMCA propagation of PrP Sc molecules in a purified system requires accessory polyanion molecules. In addition, we found that PrP Sc molecules could be formed de novo from these defined components in the absence of preexisting prions. Inoculation of samples containing either prion-seeded or spontaneously generated PrP Sc molecules into hamsters caused scrapie, which was transmissible on second passage. These results show that prions able to infect wild-type hamsters can be formed from a minimal set of components including native PrP C molecules, copurified lipid molecules, and a synthetic polyanion.

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mentioning

confidence: 99%

Formation of native prions from minimal components in vitro

Deleault¹,

Harris²,

Rees³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

585

635

View full text Add to dashboard Cite

show abstract

“…1,3 In addition, the association between TSE susceptibility and changes in the noncoding region of the PRNP gene or in putative accessory molecules have been suggested in several ovine, bovine, and murine studies. 2,9,10,14 The polymorphism at codon 132 was the only coding change observed in the open reading frame of the PRNP gene in the elk of this study. However, the four 132LL elk are progeny of long-term survivors in the heavily infected source herd, and the prolonged incubation period or protection from disease may be mediated by additional or alternative genetic factors.…”

mentioning

confidence: 54%

Preliminary Observations of Genetic Susceptibility of elk (Cervus Elaphus Nelsoni) to Chronic Wasting Disease by Experimental Oral Inoculation

Hamir

Gidlewski²,

Spraker³

et al. 2006

J VET Diagn Invest

107

125

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Abstract.To compare the genetic susceptibility of elk (Cervus elaphus nelsoni) with various alleles of the PRNP gene, which encodes the normal cellular prion protein, to chronic wasting disease (CWD), eight 8-monthold elk calves of 3 genotypes (2 132MM, 2 132LM, and 4 132LL) were orally dosed with CWD-infected brain material from elk. During postinoculation (PI) month 23, both 132MM elk had lost appetite, developed clinical signs of weight loss and central nervous system (CNS) dysfunction, and were euthanized. Two other elk (both 132LM) developed similar clinical signs of disease and were euthanized during PI month 40. All 4 affected elk had microscopic lesions of spongiform encephalopathy (SE), and PrP res , the disease-associated form of the prion protein, was detected in their CNS and lymphoid tissues by use of immunohistochemical (IHC) and Western blot (WB) techniques. These findings indicate that elk with MM and LM at codon 132 are susceptible to orally inoculated CWD. All 4 LL elk are alive at PI year 4 and are clinically normal, which suggests that 132LL elk may have reduced susceptibility to oral infection with CWD-infected material or may have prolonged incubation time.

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“…The PrP gene may be of crucial importance to disease but it is most likely not the only gene exerting influence on it. Several chromosomal regions have been associated with susceptibility [65,84], but no other gene has yet been unambiguously associated with disease.…”

Section: Introductionmentioning

confidence: 99%

PrPgenetics in ruminant transmissible spongiform encephalopathies

2008

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-Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) are prion diseases in ruminants with considerable impact on animal health and welfare. They can also pose a risk to human health and control is therefore an important issue. Prion protein (PrP) genetics may be used to control and eventually eradicate animal prion diseases. The PrP gene in sheep and other representatives of the order Artiodactyles has many polymorphisms of which several are crucial determinants of susceptibility to prion diseases, also known as transmissible spongiform encephalopathies (TSE). This review will present the current understanding of PrP genetics in ruminants highlighting similarity and difference between the species in the context of TSE.

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Quantitative Trait Loci Affecting Prion Incubation Time in Mice

Cited by 117 publications

References 42 publications

Formation of native prions from minimal components in vitro

Formation of native prions from minimal components in vitro

Preliminary Observations of Genetic Susceptibility of elk (Cervus Elaphus Nelsoni) to Chronic Wasting Disease by Experimental Oral Inoculation

PrPgenetics in ruminant transmissible spongiform encephalopathies

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