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Proc Natl Acad Sci U S A. 1994 Sep 13; 91(19): 9126–9130.

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.


Two lines of transgenic (Tg) mice expressing high (H) levels of the mutant P101L prion protein (PrP) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogenates from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD-1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximately 10% of hamsters and approximately 40% of the Tg196 mice manifested neurologic signs between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated with brain extracts, producing incubation times of approximately 400 and approximately 75 days, respectively. Although the Tg(MoPrP-P101L)H mice appear to accumulate only low levels of infections prions in their brains, the serial transmission of disease to inoculated recipients argues that prion formation occurs de novo in the brains of these uninoculated animals. These Tg mouse studies, taken together with similar findings in humans dying of inherited prion diseases, provide additional evidence that prions lack a foreign nucleic acid.

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  • Rosenthal NP, Keesey J, Crandall B, Brown WJ. Familial neurological disease associated with spongiform encephalopathy. Arch Neurol. 1976 Apr;33(4):252–259. [PubMed]
  • Masters CL, Gajdusek DC, Gibbs CJ., Jr Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain. 1981 Sep;104(3):559–588. [PubMed]
  • Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature. 1989 Mar 23;338(6213):342–345. [PubMed]
  • Petersen RB, Tabaton M, Berg L, Schrank B, Torack RM, Leal S, Julien J, Vital C, Deleplanque B, Pendlebury WW, et al. Analysis of the prion protein gene in thalamic dementia. Neurology. 1992 Oct;42(10):1859–1863. [PubMed]
  • Poulter M, Baker HF, Frith CD, Leach M, Lofthouse R, Ridley RM, Shah T, Owen F, Collinge J, Brown J, et al. Inherited prion disease with 144 base pair gene insertion. 1. Genealogical and molecular studies. Brain. 1992 Jun;115(Pt 3):675–685. [PubMed]
  • Dlouhy SR, Hsiao K, Farlow MR, Foroud T, Conneally PM, Johnson P, Prusiner SB, Hodes ME, Ghetti B. Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. Nat Genet. 1992 Apr;1(1):64–67. [PubMed]
  • Gabizon R, Rosenmann H, Meiner Z, Kahana I, Kahana E, Shugart Y, Ott J, Prusiner SB. Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD). Am J Hum Genet. 1993 Oct;53(4):828–835. [PMC free article] [PubMed]
  • Prusiner SB. Molecular biology of prion diseases. Science. 1991 Jun 14;252(5012):1515–1522. [PubMed]
  • Basler K, Oesch B, Scott M, Westaway D, Wälchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 1986 Aug 1;46(3):417–428. [PubMed]
  • Oesch B, Westaway D, Wälchli M, McKinley MP, Kent SB, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE, et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985 Apr;40(4):735–746. [PubMed]
  • Chesebro B, Race R, Wehrly K, Nishio J, Bloom M, Lechner D, Bergstrom S, Robbins K, Mayer L, Keith JM, et al. Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature. 1985 May 23;315(6017):331–333. [PubMed]
  • Bockman JM, Kingsbury DT, McKinley MP, Bendheim PE, Prusiner SB. Creutzfeldt-Jakob disease prion proteins in human brains. N Engl J Med. 1985 Jan 10;312(2):73–78. [PubMed]
  • Brown P, Coker-Vann M, Pomeroy K, Franko M, Asher DM, Gibbs CJ, Jr, Gajdusek DC. Diagnosis of Creutzfeldt-Jakob disease by Western blot identification of marker protein in human brain tissue. N Engl J Med. 1986 Feb 27;314(9):547–551. [PubMed]
  • Bockman JM, Prusiner SB, Tateishi J, Kingsbury DT. Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes. Ann Neurol. 1987 Jun;21(6):589–595. [PubMed]
  • Serban D, Taraboulos A, DeArmond SJ, Prusiner SB. Rapid detection of Creutzfeldt-Jakob disease and scrapie prion proteins. Neurology. 1990 Jan;40(1):110–117. [PubMed]
  • Brown P, Goldfarb LG, McCombie WR, Nieto A, Squillacote D, Sheremata W, Little BW, Godec MS, Gibbs CJ, Jr, Gajdusek DC. Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. Neurology. 1992 Feb;42(2):422–427. [PubMed]
  • Medori R, Montagna P, Tritschler HJ, LeBlanc A, Cortelli P, Tinuper P, Lugaresi E, Gambetti P. Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology. 1992 Mar;42(3 Pt 1):669–670. [PubMed]
  • Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE, et al. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10962–10966. [PMC free article] [PubMed]
  • Kitamoto T, Tateishi J, Tashima T, Takeshita I, Barry RA, DeArmond SJ, Prusiner SB. Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies. Ann Neurol. 1986 Aug;20(2):204–208. [PubMed]
  • Roberts GW, Lofthouse R, Allsop D, Landon M, Kidd M, Prusiner SB, Crow TJ. CNS amyloid proteins in neurodegenerative diseases. Neurology. 1988 Oct;38(10):1534–1540. [PubMed]
  • Tagliavini F, Prelli F, Ghiso J, Bugiani O, Serban D, Prusiner SB, Farlow MR, Ghetti B, Frangione B. Amyloid protein of Gerstmann-Sträussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J. 1991 Mar;10(3):513–519. [PMC free article] [PubMed]
  • Carlson GA, Ebeling C, Yang SL, Telling G, Torchia M, Groth D, Westaway D, DeArmond SJ, Prusiner SB. Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5690–5694. [PMC free article] [PubMed]
  • Mendell JR, Sahenk Z, Gales T, Paul L. Amyloid filaments in inclusion body myositis. Novel findings provide insight into nature of filaments. Arch Neurol. 1991 Dec;48(12):1229–1234. [PubMed]
  • Muramoto T, Kitamoto T, Tateishi J, Goto I. The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease. Am J Pathol. 1992 Jun;140(6):1411–1420. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Hsiao KK, Scott M, Foster D, Groth DF, DeArmond SJ, Prusiner SB. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 1990 Dec 14;250(4987):1587–1590. [PubMed]
  • Akowitz A, Sklaviadis T, Manuelidis L. Endogenous viral complexes with long RNA cosediment with the agent of Creutzfeldt-Jakob disease. Nucleic Acids Res. 1994 Mar 25;22(6):1101–1107. [PMC free article] [PubMed]
  • KLATZO I, GAJDUSEK DC, ZIGAS V. Pathology of Kuru. Lab Invest. 1959 Jul-Aug;8(4):799–847. [PubMed]
  • Taraboulos A, Jendroska K, Serban D, Yang SL, DeArmond SJ, Prusiner SB. Regional mapping of prion proteins in brain. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7620–7624. [PMC free article] [PubMed]
  • Alper T, Cramp WA, Haig DA, Clarke MC. Does the agent of scrapie replicate without nucleic acid? Nature. 1967 May 20;214(5090):764–766. [PubMed]
  • Diener TO, McKinley MP, Prusiner SB. Viroids and prions. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5220–5224. [PMC free article] [PubMed]
  • Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. [PubMed]
  • Bellinger-Kawahara C, Diener TO, McKinley MP, Groth DF, Smith DR, Prusiner SB. Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids. Virology. 1987 Sep;160(1):271–274. [PubMed]
  • Kellings K, Meyer N, Mirenda C, Prusiner SB, Riesner D. Further analysis of nucleic acids in purified scrapie prion preparations by improved return refocusing gel electrophoresis. J Gen Virol. 1992 Apr;73(Pt 4):1025–1029. [PubMed]
  • Chesebro B, Caughey B. Scrapie agent reflication without the prion protein? Curr Biol. 1993 Oct 1;3(10):696–698. [PubMed]
  • Ozel M, Diringer H. Small virus-like structure in fractions from scrapie hamster brain. Lancet. 1994 Apr 9;343(8902):894–895. [PubMed]

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