Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication

Prusiner, Stanley B.; Scott, Michael; Foster, Dallas; Pan, Keh-Ming; Groth, Darlene; Mirenda, C.; Torchia, Marilyn; Yang, Shu-Lian; Serban, Dan; Carlson, George A.; Hoppe, Peter C.; Westaway, David; DeArmond, Stephen J.

doi:10.1016/0092-8674(90)90134-z

Cited by 825 publications

(569 citation statements)

References 74 publications

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“…Based on the name given to such a protein-based nucleic-acid free agent, a proteinaceous infectious particle or prion, the protein was called the prion protein (PrP). Further pathological studies showed that the typical, often fibrillar, amyloid deposits, found in the brains of inoculated individuals, contained host-encoded PrP [6]. Together, these findings sparked wide-ranging studies on PrP, both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 95%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

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Section: Introductionmentioning

confidence: 95%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

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“…In the case of certain mutations in PrP c, spontaneous conversion to PrP sc may occur as a rare event, explaining why familial CJD or GSS arise spontaneously, albeit late in life. Sporadic CJD may come about when an extremely rare event (occurring in one among a million individuals per year) leads to spontaneous conversion of PrP c to PrP s~ and gives rise to a conversion cascade [10,35]. (b).…”

Section: Biosynthesis Of Prp C and Prp Scmentioning

confidence: 99%

“…In the case of prion transmission from hamsters to mice, this so-called species barrier was overcome by introducing hamster Prnp transgenes into recipient wild-type mice [34,35]. Importantly, the properties of the prions produced in these transgenic mice corresponded to the prion species used for inoculation [35], that is, infection with hamster prions led to production of hamster prions but infection with mouse prions gave rise to mouse prions. Within the framework of the 'protein only' hypothesis this means that hamster PrP c but not murine PrP c (which differs from the former by 10 amino acids), is a suitable substrate for conversion to hamster PrP sc by hamster prions and vice versa.…”

Section: Genetic Evidence Linking the Prp Gene With Prion Diseasementioning

confidence: 99%

Molecular biology of transmissible spongiform encephalopathies

1996

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The prion, the transmissible agent that causes spongiform encephalopathies such as serapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease, is believed to be devoid of nucleic acid and identical with PrP so, a modified form of the normal host protein PrP ¢ which is encoded by the single cop~v gene Prnp. The 'protein only" hypothesis proposes that PrP ~c, when introduced into a normal host, causes the conversion of PrP c into prpS~; it therefore predicts that an animal devoid of PrP c should be resistant to prion diseases. We generated homozygous Prnp °1° ('PrP knockout') mice and showed that, after inoculation with prions, they remained free of scrapie for at least 2 years while wild-type controls all died within 6 months. There was no propagation of prions in the Prnp °t° animals. Surprisingly, heterozygous Prnp °t+ mice, which express PrP c at about half the normal level, also showed enhanced resistance to scrapie disease despite high levels of infectious agent and PrP ~c in the brain early on. After introduction of murine PrP transgenes Prnp °t° mice became highly susceptible to mouse but not to hamster prions, while the insertion of Syrian hamster PrP transgenes rendered them susceptible to hamster but to a much lesser extent to mouse prions. These complementation experiments paved the way to the application of reverse genetics. We have prepared animals transgenic for genes encoding PrP with amino terminal deletions of various lengths and have found that PrP lacking 48 amino proximal amino acids, which comprise four of the five octa repeats of PrP, is still biologically active.

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“…Insgesamt sind mit einem Verhältnis von 1,4:1 mehr Frauen als Männer betroffen , Heinemann et al 2007a (Prusiner et al 1990). …”

Section: Die Sporadische Creutzfeldt-jakob-krankheitunclassified

Risikofaktoren der sporadischen Creutzfeldt-Jakob-Krankheit

Kittner

Heinemann

Zerr

2009

Dtsch med Wochenschr

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Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication

Cited by 825 publications

References 74 publications

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Molecular biology of transmissible spongiform encephalopathies

Risikofaktoren der sporadischen Creutzfeldt-Jakob-Krankheit

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