Abstract
PrP 27-30, a unique protease-resistant protein associated with scrapie infectivity, derives from the proteolytic cleavage of a larger precursor encoded by a host gene. To identify sites of PrP biosynthesis, in situ hybridization was done using cloned PrP cDNA as a probe. In rodent brain, PrP mRNA was expressed in neurons, ependymal cells, choroid plexus epithelium, astrocytes, pericytes, endothelial cells and meninges of both scrapie-infected and uninfected animals. PrP mRNA was also detected in vitro in isolated brain microglia cells. Pulmonary cells and heart muscle cells contained high levels of this mRNA. Hybridization was not detected in spleen, confirming earlier RNA blot experiments indicating extremely low levels of PrP mRNA in this tissue. Results indicate that PrP mRNA is a normal component in a variety of non-neuronal tissues and may explain the origin of the amyloid plaques present in the subependymal region of scrapie-infected brain.
MeSH Terms
Animals
Brain/metabolism,pathology
DNA/metabolism
Gene Expression Regulation
Mice
Mice, Inbred C57BL
Nucleic Acid Hybridization
PrP 27-30 Protein
RNA, Messenger/genetics,metabolism
Scrapie/metabolism,pathology
Viral Proteins/genetics,metabolism
Chemicals
RNA, Messenger
Viral Proteins
PrP 27-30 Protein
DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Brown H R
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Goller N L
Rudelli R D
Merz G S
Wolfe G C
Wisniewski H M
Robakis N K
References (31)
31 references, click to expand
-
Amyloid plaques in the brains of mice with Creutzfeldt-Jakob disease.
Ann Neurol. 1984 Mar;15(3):278-80
PMID: 6372648
-
A membrane-filter technique for the detection of complementary DNA.
Biochem Biophys Res Commun. 1966 Jun 13;23(5):641-6
PMID: 5963888
-
Scrapie prions aggregate to form amyloid-like birefringent rods.
Cell. 1983 Dec;35(2 Pt 1):349-58
PMID: 6418385
-
Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues.
Proc Natl Acad Sci U S A. 1986 Sep;83(17):6377-81
PMID: 3529083
-
Changes in the localization of brain prion proteins during scrapie infection.
Neurology. 1987 Aug;37(8):1271-80
PMID: 3112607
-
Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.
Proc Natl Acad Sci U S A. 1978 Dec;75(12):6268-70
PMID: 104301
-
Viroids and prions.
Proc Natl Acad Sci U S A. 1982 Sep;79(17):5220-4
PMID: 6813855
-
Pathogenesis of mouse scrapie: distribution of agent in the pulp and stroma of infected spleens.
Vet Microbiol. 1984 Jul;9(3):215-25
PMID: 6433538
-
Effect of route of infection on the frequency and distribution of cerebral amyloid plaques in scrapie mice.
Neuropathol Appl Neurobiol. 1981 Jul-Aug;7(4):289-98
PMID: 7197001
-
Pathogenesis of scrapie virus infection in the mouse.
J Infect Dis. 1967 Feb;117(1):15-22
PMID: 4961240
-
Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating.
Histochemistry. 1983;77(2):275-9
PMID: 6188729
-
Identification of a protein that purifies with the scrapie prion.
Science. 1982 Dec 24;218(4579):1309-11
PMID: 6815801
-
Localization of a human gene homologous to the PrP gene on the p arm of chromosome 20 and detection of PrP-related antigens in normal human brain.
Biochem Biophys Res Commun. 1986 Oct 30;140(2):758-65
PMID: 2877664
-
Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain.
Nature. 1985 May 23-29;315(6017):331-3
PMID: 3923361
-
Detection of prion protein mRNA in normal and scrapie-infected tissues and cell lines.
J Gen Virol. 1988 Mar;69 ( Pt 3):711-6
PMID: 2895163
-
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):559-88
PMID: 6791762
-
Observations of amyloid angiopathy and senile plaques by the scanning electron microscope.
Acta Neuropathol. 1979 Nov;48(2):153-6
PMID: 506698
-
Antibodies to a scrapie prion protein.
Nature. 1984 Aug 2-8;310(5976):418-21
PMID: 6431296
-
Identification of prion amyloid filaments in scrapie-infected brain.
Cell. 1985 May;41(1):221-35
PMID: 3922627
-
Unconventional viruses and the origin and disappearance of kuru.
Science. 1977 Sep 2;197(4307):943-60
PMID: 142303
-
Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination.
Intervirology. 1984;21(2):61-9
PMID: 6421769
-
Abnormal fibrils from scrapie-infected brain.
Acta Neuropathol. 1981;54(1):63-74
PMID: 7195134
-
Requirement of a protein component for scrapie infectivity.
Intervirology. 1980;14(3-4):213-6
PMID: 6786997
-
Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy.
J Histochem Cytochem. 1974 Dec;22(12):1077-83
PMID: 4374474
-
Pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titres and scrapie-associated fibrils in brains of hamsters infected intraperitoneally.
J Gen Virol. 1986 Sep;67 ( Pt 9):2005-9
PMID: 2875123
-
Scrapie prion proteins are synthesized in neurons.
Am J Pathol. 1986 Jan;122(1):1-5
PMID: 3079955
-
Isolation and characterization of macrophages from scrapie-infected mouse brain.
Acta Neuropathol. 1987;72 (3):240-7
PMID: 3031922
-
Scrapie infectivity, fibrils and low molecular weight protein.
Nature. 1983 Dec 1-7;306(5942):476-8
PMID: 6685822
-
Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene.
Cell. 1986 Aug 1;46(3):417-28
PMID: 2873895
-
Comparison of scrapie and transmissible mink encephalopathy in hamsters. II. Clinical signs, pathology, and pathogenesis.
J Infect Dis. 1975 Feb;131(2):104-10
PMID: 1167884
-
A cellular gene encodes scrapie PrP 27-30 protein.
Cell. 1985 Apr;40(4):735-46
PMID: 2859120