Spontaneous generation of rapidly transmissible prions in transgenic mice expressing wild-type bank vole prion protein.

Proceedings of the National Academy of Sciences of the United States of America
Joel C WattsS B Prusiner

Abstract

Currently, there are no animal models of the most common human prion disorder, sporadic Creutzfeldt-Jakob disease (CJD), in which prions are formed spontaneously from wild-type (WT) prion protein (PrP). Interestingly, bank voles (BV) exhibit an unprecedented promiscuity for diverse prion isolates, arguing that bank vole PrP (BVPrP) may be inherently prone to adopting misfolded conformations. Therefore, we constructed transgenic (Tg) mice expressing WT BVPrP. Tg(BVPrP) mice developed spontaneous CNS dysfunction between 108 and 340 d of age and recapitulated the hallmarks of prion disease, including spongiform degeneration, pronounced astrogliosis, and deposition of alternatively folded PrP in the brain. Brain homogenates of ill Tg(BVPrP) mice transmitted disease to Tg(BVPrP) mice in ∼35 d, to Tg mice overexpressing mouse PrP in under 100 d, and to WT mice in ∼185 d. Our studies demonstrate experimentally that WT PrP can spontaneously form infectious prions in vivo. Thus, Tg(BVPrP) mice may be useful for studying the spontaneous formation of prions, and thus may provide insight into the etiology of sporadic CJD.

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Citations

Nov 28, 2013·Annual Review of Genetics·Stanley B Prusiner
Jan 8, 2014·Disease Models & Mechanisms·Walker S Jackson
Apr 5, 2014·PLoS Pathogens·Joel C WattsStanley B Prusiner
Nov 14, 2013·International Journal of Cell Biology·Isabelle Acquatella-Tran Van BaVéronique Perrier
Aug 24, 2013·Research in Veterinary Science·J SadeghinezhadR Chiocchetti
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Jun 23, 2015·Annals of Neurology·Joel C WattsStanley B Prusiner
Jul 8, 2014·The Biochemical Journal·Alana M ThackrayRaymond Bujdoso
May 30, 2015·Acta Neuropathologica·Atsushi KobayashiTetsuyuki Kitamoto
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Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Walker S JacksonSusan Lindquist
Nov 21, 2014·PLoS Pathogens·Walker S Jackson, Clemens Krost
Jun 29, 2016·Acta Neuropathologica·Joel C WattsStanley B Prusiner
Jan 14, 2017·Acta Neuropathologica·Sebastian Brandner, Zane Jaunmuktane
Feb 8, 2018·Pathogens·Holger Wille, Jesús R Requena
Jan 6, 2018·Pathogens·Angélique Igel-EgalonPierre Sibille
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May 9, 2014·Journal of Virology·Alana M ThackrayRaymond Bujdoso
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Jul 28, 2018·Brain Pathology·Atsushi KobayashiTetsuyuki Kitamoto
Mar 26, 2019·PLoS Pathogens·Cassandra M BurkeSurachai Supattapone
May 27, 2014·The Journal of Biological Chemistry·Joel C Watts, Stanley B Prusiner
Dec 29, 2018·Molecular Neurobiology·Chafik HarrathiJoaquín Castilla
Mar 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jatish KumarLuis M Liz-Marzán
Jan 18, 2017·Cold Spring Harbor Perspectives in Medicine·Joel C Watts, Stanley B Prusiner
Sep 21, 2019·Annual Review of Genetics·Simon MeadJohn Collinge
Nov 3, 2017·Acta Neuropathologica·Natalia Fernández-BorgesJoaquín Castilla

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