ACCESSION NO: IND20532193
AUTHOR: Lasmezas, C.I. Deslys, J.P. Demaimay, R. Adjou, K.T.
Hauw, J.J. Dormont, D.
TITLE: Strain specific and common pathogenic events in murine models
of scrapie and bovine spongiform encephalopathy.
SOURCE: The Journal of general virology. July 1996. v. 77 (pt.7) p.
1601-1609.
PUBLISHER: Reading : Society for General Microbiology.
STATE/COUNTRY: England
DATE: 1996 07
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0022-1317
ABSTRACTS: The development of transmissible spongiform encephalopathies
in experimental models depends on two major factors: the
intracerebral accumulation of an abnormal, protease-resistant
isoform of PrP (PrP(res)), which is a host protein mainly
expressed in neurons; and the existence of different strains
of agent. In order to make a distinction between pathogenic
mechanisms depending upon the accumulation of host-derived
PrPr(res) and the strain-specific effects, we quantified and
compared the sequence of molecular [PrP(res) and glial
fibrillary acidic protein (GFAP) accumulation] and
pathological events in the brains of syngeneic mice
throughout the course of infection with two different strains
of agent. The bovine spongiform encephalopathy (BSE) agent
exhibits properties different from any known scrapie source
and has been studied in comparison with a classical scrapie
strain. Convergent kinetic data in both models confirmed the
cause-effect relationship between PrP(res) and pathological
changes and showed that PrP(res) accumulation is directly
responsible for astrocyte activation in vivo. Moreover, we
observed a threshold level of PrP(res) for this effect on
astroglial cells. However, despite similar infectivity
titres, the BSE model produced less PrP(res) than scrapie,
and the relative importance of gliosis was higher. The
comparison of the molecular and pathological features after
intracerebral or intraperitoneal inoculation also revealed
differences between the models. Therefore, the mechanisms
leading to the targeting and the fine regulation of the
molecular events seem to be independent of the host PrP and
to depend upon the agent. The possible involvement of a
regulatory molecule accounting for these specificities has to
be considered.
IDENTIFIERS: Protease resistant isoform of prion protein; Glial fibrillary
acidic protein; Mice.; Scrapie agent.; Scrapie.; Bovine
spongiform encephalopathy.; Pathogenesis.; Strains.; Prions.;
Animal models.; Animal proteins.; Experimental infections.;
Brain.; Histopathology.
SUBJ CATEGORY: L833 ANIMAL DISEASES, VIRAL
L840 ANIMAL DISEASES, PHYSIOLOGICAL
ACCESSION NO: IND20531226
AUTHOR: Mestel, R.
TITLE: Putting prions to the test.
SOURCE: Science. July 12, 1996. v. 273 (5272) p. 184-189.
PUBLISHER: Washington, D.C. : American Association for the Advancement
of Science.
STATE/COUNTRY: District of Columbia
SOURCE AUTHOR: Science (Weekly).
DATE: 1996 0712
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: US Imprint, not USDA
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0036-8075
IDENTIFIERS: Prions.; Proteins.; Infectious diseases.; Human diseases.;
Animal diseases.; Theory.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
X380 HUMAN MEDICINE
ACCESSION NO: IND20530153
AUTHOR: Fischer, M. Rulicke, T. Raeber, A. Sailer, A. Moser, M.
Oesch, B. Brandner, S. Aguzzi, A. Weissmann, C.
TITLE: Prion protein (PrP) with amino-proximal deletions restoring
susceptibility of PrP knockout mice to scrapie.
SOURCE: The EMBO journal. Mar 15, 1996. v. 15 (6) p. 1255-1264.
PUBLISHER: Oxford, U.K. : Oxford University Press.
STATE/COUNTRY: England
DATE: 1996 0315
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0261-4189
ABSTRACTS: The 'protein only' hypothesis postulates that the prion, the
agent causing transmissible spongiform encephalopathies, is
PrPSc, an isoform of the host protein PrPC. Protease
treatment of prion preparations cleaves off approximately 60
N-terminal residues of PrPSc but does not abrogate
infectivity. Disruption of the PrP gene in the mouse
abolishes susceptibility to scrapie and prion replication. We
have introduced into PrP knockout mice transgenes encoding
wild-type PrP or PrP lacking 26 or 49 amino-proximal amino
acids which are protease susceptible in PrPSC. Inoculation
with prions led to fatal disease, prion propagation and
accumulation of PrPSc in mice expressing both wild-type and
truncated PrPs. Within the framework of the 'protein only'
hypothesis, this means that the amino-proximal segment of
PrPC is not required either for its susceptibility to
conversion into the pathogenic, infectious form of PrP or for
the generation of PrPSc.
IDENTIFIERS: Mice.; Animal proteins.; Deletions.; Susceptibility.;
Scrapie.; Prions.; Infectivity.; Transgenic animals.;
Mutants.; Gene expression.; Messenger rna.
SUBJ CATEGORY: L833 ANIMAL DISEASES, VIRAL
L200 ANIMAL GENETICS
ACCESSION NO: IND20529667
AUTHOR: Riek, R. Hornemann, S. Wider, G. Billeter, M.
Glockshuber, R. Wuthrich, K.
TITLE: NMR structure of the mouse prion protein domain Prp(121-231).
SOURCE: Nature. July 11, 1996. v. 382 (6587) p. 180-182.
PUBLISHER: London : Macmillan Magazines Ltd.
STATE/COUNTRY: England
SOURCE AUTHOR: Nature (London, England).
DATE: 1996 0711
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0028-0836
ABSTRACTS: The 'protein only' hypothesis states that a modified form of
normal prion protein triggers infectious neurodegenerative
diseases, such as bovine spongiform encephalopathy (BSE), or
Creutzfeldt-Jakob disease (CJD) in humans. Prion proteins are
thought to exist in two different conformations: the 'benign'
PrP(c) form, and the infectious 'scrapie form', PrP(Sc).
Knowledge of the three-dimensional structure of PrP(c) is
essential for understanding the transition to PrP(Sc). The
nuclear magnetic resonance (NMR) structure of the
autonomously folding PrP domain comprising residues 121-231
(ref. 6) contains a two-stranded antiparallel beta-sheet and
three alpha-helices. This domain contains most of the point-
mutation sites that have been linked, in human PrP, to the
occurrence of familial prion diseases. The NMR structure
shows that these mutations occur within, or directly adjacent
to, regular secondary structures. The presence of a beta-
sheet in PrP(121-231) is in contrast with model predictions
of an all-helical structure of PrP(c) (ref. 8), and may be
important for the initiation of the transition from PrP(c) to
PrP(Sc).
IDENTIFIERS: Prions.; Proteins.; Nuclear magnetic resonance.; Mice.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
L600 ANIMAL PHYSIOLOGY AND BIOCHEMISTRY
ACCESSION NO: IND20509134
AUTHOR: Priola, S.A. Caughey, B. Wehrly, K. Chesebro, B.
TITLE: A 60-kDa prion protein (PrP) with properties of both the
normal and scrapie-associated forms of PrP.
SOURCE: The Journal of biological chemistry. Feb 17, 1995. v. 270
(7) p. 3299-3305.
PUBLISHER: Bethesda, Md. : American Society for Biochemistry and
Molecular Biology.
STATE/COUNTRY: Maryland
DATE: 1995 0217
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: US Imprint, not USDA
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0021-9258
ABSTRACTS: Scrapie is a transmissible spongiform encephalopathy of sheep
and other mammals in which disease appears to be caused by
the accumulation of an abnormal form of a host protein, prion
protein (PrP), in the brain and other tissues. The process by
which the normal protease-sensitive form of PrP is converted
into the abnormal protease-resistant form is unknown. Several
hypotheses predict that oligomeric forms of either the normal
or abnormal PrP may act as intermediates in the conversion
process. We have now identified a 60-kDa PrP derived from
hamster PrP expressed in murine neuroblastoma cell. Peptide
mapping studies provided evidence that the 60-kDa PrP was
composed solely of PrP and, based on its molecular mass,
appeared to be a PrP dimer. The 60-kDa PrP was not
dissociated under several harsh denaturing conditions, which
indicated that it was covalently linked. It was similar to
the disease-associated form of PrP in that it formed large
aggregates. However, it resembled the normal form of PrP in
that it was sensitive to proteinase K and had a short
metabolic half-life. The 60-kDa PrP, therefore, had
characteristics of both the normal and disease-associated
form of PrP. Formation and aggregation of the 60-kDa hamster
PrP occurs in uninfected mouse neuroblastoma cell, which
suggests that hamster PrP has a predisposition to aggregate
even in the absence of scrapie infectivity. Similar 60-kDa
PrP bands were identified in scrapie-infected hamster brain
but not in uninfected brain. Therefore, a 60-kDa molecule
might participate in the scrapie-associated conversion of
protease-sensitive PrP to protease-resistant PrP.
IDENTIFIERS: Protein subunits; Prions.; Proteins.; Extraction.;
Proteinases.; Immunoprecipitation tests.; Molecular weight.;
Biosynthesis.; Cell lines.; Hamsters.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
ACCESSION NO: IND20452334
AUTHOR: Hunter, N. u BBSRC/MRC, Edinburgh, U.K. Goldmann, W. Smith,
G. Hope, J.
TITLE: The association of a codon 136 PrP gene variant with the
occurrence of natural scrapie.
SOURCE: Archives of virology. 1994. v. 137 (1/2) p. 171-177.
PUBLISHER: Wien, Austria : Springer-Verlag.
STATE/COUNTRY: Austria
DATE: 1994
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0304-8608
ABSTRACTS: Incidence of both experimental and natural scrapie in sheep
has been associated with polymorphisms of the PrP gene. In
case/control studies the PrP allele which encodes valine at
codon 136 (Val136) is found in 96-100% of naturally infected
scrapie sheep of Shetland, Scottish Halfbred and Bleu du
Maine breeds. In contrast, in healthy animals from the same
flocks, the most frequent allele encodes Ala136 (91-100% of
sheep). However Val136 does not correlate with incidence of
scrapie in two other flocks--Poll Dorsets and Suffolks and
there may therefore be breed differences in PrP genotypes
affected by scrapie.
IDENTIFIERS: Sheep.; Scrapie.; Nucleotide sequences.; Prions.;
Susceptibility.; Breed differences.; Genotypes.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
L200 ANIMAL GENETICS
ACCESSION NO: IND20448561
AUTHOR: Groschup, M.H. u Federal Reserve Centre for Virus Diseases of
Animals, Tubingen, Federal Republic of Germany. Langeveld,
J. Pfaff, E.
TITLE: The major species specific epitope in prion proteins of
ruminants.
SOURCE: Archives of virology. 1994. v. 136 (3/4) p. 423-431.
PUBLISHER: Wien, Austria : Springer-Verlag.
STATE/COUNTRY: Austria
DATE: 1994
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0304-8608
ABSTRACTS: The species specific nature of an antigenic determinant
previously discovered in the scrapie form of prion protein
(PrPD) from cattle, sheep and mice, was further investigated
in normal prion protein (PrPC) from these and other species.
This was carried out with eight different anti-peptide sera
raised in rabbits against various synthetic peptides
representing segments of the amino acid (aa) sequence 101-122
of ovine, bovine, murine and hamster PrP. Antipeptide serum
against a peptide representing aa 107-122 of ovine PrP showed
almost specific reaction and crossreacted in immunoblot with
caprine and human PrP only. Antisera to the corresponding
bovine sequence stained bovine and porcine PrP and to a minor
extent PrP of goat, man, cat, and mink, while antiserum to
the murine aa sequence reacted with rodent and monkey PrP
only. In contrast, antiserum to the corresponding hamster
sequence displayed a broader reactivity pattern, just like
the four other anti-peptide sera to various ovine and bovine
sequences. Antisera were also tested for reactivity with the
pathogenic isoforms of PrP of sheep, cow, hamster and mouse
and showed generally similar reactivity patterns as by using
PrPC. In conclusion, the region close to the actual or
putative proteinase K cleavage sites of PrP seems to exhibit
high structural variability among mammalian species.
IDENTIFIERS: Animal proteins.; Prions.; Species differences.; Antigenic
determinants.; Immunoblotting.; Antibodies.; Amino acid
sequences.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
L200 ANIMAL GENETICS
ACCESSION NO: IND20435048
AUTHOR: Fairbairn, D.W. u Brigham Young University, Provo, UT.
Thwaits, R.N. Holyoak, G.R. O'Neil, K.L.
TITLE: Spongiform encephalopathies and prions: an overview of
pathology and disease mechanisms.
SOURCE: FEMS microbiology letters. Nov 1, 1994. v. 123 (3) p. 233-
239.
PUBLISHER: Amsterdam, The Netherlands : Elsevier Science Publishers.
STATE/COUNTRY: Netherlands
SOURCE AUTHOR: Federation of European Microbiological Societies..
DATE: 1994 1101
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: Non-US Imprint, not FAO
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0378-1097
ABSTRACTS: The etiology of spongiform encephalopathies has been sharply
contested for decades. At the heart of the issue is the
question of disease origin: Are prion diseases representative
of primary neurodegenerative genetic disorders, or are they
bona fide infectious diseases? This article provides a brief
outline of the progress made in the elucidation of prion
disease mechanisms in the context of pathological support of
the 'protein only' hypothesis. The answer to the above
question appears to be that spongiform encephalopathies are
uniquely both infectious and genetic neurodegenerative
diseases.
IDENTIFIERS: Bovine spongiform encephalopathy.; Spongiform
encephalopathy.; Prions.; Scrapie agent.; Proteins.; Genes.;
Infectivity.; Infectious diseases.; Hereditary diseases.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
L840 ANIMAL DISEASES, PHYSIOLOGICAL
X380 HUMAN MEDICINE
ACCESSION NO: IND20434384
AUTHOR: Prusiner, S.B.
TITLE: Biology and genetics of prion diseases.
SOURCE: Annual review of microbiology. 1994. v. 48 p. 655-686.
PUBLISHER: Palo Alto, Calif. : Annual Reviews, Inc.
STATE/COUNTRY: California
DATE: 1994
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: US Imprint, not USDA
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0066-4227
IDENTIFIERS: Prions.; Scrapie agent.; Diseases.; Proteins.; Genetics.;
Transgenics.; Mice.
SUBJ CATEGORY: L830 ANIMAL DISEASES, GENERAL
X380 HUMAN MEDICINE
ACCESSION NO: IND20380398
AUTHOR: Safar, J. Roller, P.P. Gajdusek, D.C. Gibbs, C.J. Jr.
TITLE: Conformational transitions, dissociation, and unfolding of
scrapie amyloid (prion) protein.
SOURCE: The Journal of biological chemistry. Sept 25, 1993. v. 268
(27) p. 20276-20284.
PUBLISHER: Baltimore, Md. : American Society for Biochemistry and
Molecular Biology.
STATE/COUNTRY: Maryland
DATE: 1993 0925
LANGUAGE: English
PUB TYPE: Article
PUB AGENCY: US Imprint, not USDA
SUBFILE/LOCAT: DNAL IND
STANDARD NO: ISSN: 0021-9258
ABSTRACTS: The infectious form of the scrapie amyloid (prion) precursor,
PrP(Sc), is a host-derived protein and a component of the
infectious agent causing scrapie. PrP(Sc) and the carboxyl-
terminal proteinase K resistant core, PrP27-30, have the
potential to form amyloid as a result of a post-
translational event or conformational abnormality. We have
studied the conformational transitions of both proteins
reconstituted into liposomes, associated in solid state in
thin films, and dissociated by guanidine HCl. The secondary
structure of PrP(Sc) in liposomes deduced from analysis of
circular dichroism spectra contained approximately 34% beta-
sheets, approximately 20% alpha-helix, and approximately
46%,8-turns and random coil. Cleavage of the amino-terminal
region of PrP(Sc) resulted in all-beta PrP27-30, with an
estimated approximate 43% beta-sheet, no alpha-helix, and
approximately 57% beta-turns and random coil. The PrP(Sc)
associated in thin films with a tertiary structure
perturbation corresponding to unfolding, while the secondary
structure was preserved. The PrP27-30 assembled into the
solid state with a similar perturbation of tertiary
structure but with a large increase in the beta-sheet
content, probably due to an intermolecular alignment of the
external beta-sheets, or to a secondary structure transition,
or both. The various conformational states had little or no
impact on infectivity. Equilibrium dissociation and
unfolding demonstrated a greater resistance of PrP27-30 to
denaturation. The dissociated monomers unfolded through
intermediate(s), suggesting the presence of protein domains
with distinct secondary structure stabilities. The results
provide experimental evidence for the beta-sheet type
assembly of scrapie amyloid PrP27-30 in the solid state and
demonstrate the importance of amino-terminal cleavage in
the stability and alignment of the amyloid-forming
monomers.
IDENTIFIERS: Secondary structure; Scrapie agent.; Prions.; Viral
proteins.; Molecular conformation.; Amyloid.
SUBJ CATEGORY: L833 ANIMAL DISEASES, VIRAL