title: Gene expression in scrapie. Cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts.
abstract: To define genes associated with or responsible for the neurodegenerative changes observed in transmissible spongiform encephalopathies, we analyzed gene expression in scrapie-infected mouse brain using "mRNA differential display." The RNA transcripts of eight genes were increased 3-8-fold in the brains of scrapie-infected animals. Five of these genes have not previously been reported to exhibit increased expression in this disease: cathepsin S, the C1q B-chain of complement, apolipoprotein D, and two previously unidentified genes denominated scrapie-responsive gene (ScRG)-1 and ScRG-2, which are preferentially expressed in brain tissue. Increased expression of the three remaining genes, beta2 microglobulin, F4/80, and metallothionein II, has previously been reported to occur in experimental scrapie. Kinetic analysis revealed a concomitant increase in the levels of ScRG-1, cathepsin S, the C1q B-chain of complement, and beta2 microglobulin mRNA as well as glial fibrillary acidic protein and F4/80 transcripts, markers of astrocytosis and microglial activation, respectively. In contrast, the level of ScRG-2, apolipoprotein D, and metallothionein II mRNA was only increased at the terminal stage of the disease. ScRG-1 mRNA was found to be preferentially expressed in glial cells and to code for a short protein of 47 amino acids with a strong hydrophobic N-terminal region.
authors.affiliation: Laboratoire d'Oncologie Virale CNRS UPR 9045, IFC1, 94801 Villejuif cedex France.
authors.forename: F
authors.initials: F
authors.lastname: Dandoy-Dron
authors.forename: F
authors.initials: F
authors.lastname: Guillo
authors.forename: L
authors.initials: L
authors.lastname: Benboudjema
authors.forename: J P
authors.initials: JP
authors.lastname: Deslys
authors.forename: C
authors.initials: C
authors.lastname: Lasmézas
authors.forename: D
authors.initials: D
authors.lastname: Dormont
authors.forename: M G
authors.initials: MG
authors.lastname: Tovey
authors.forename: M
authors.initials: M
authors.lastname: Dron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D053399:Apolipoproteins D; D001483:Base Sequence; D001921:Brain / Q000821:virology; D002403:Cathepsins / Q000235:genetics; D003001:Cloning, Molecular; D015922:Complement C1q / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012608:Scrapie / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D001053:Apolipoproteins; D053399:Apolipoproteins D; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C111496:Scrg1 protein, mouse; D015922:Complement C1q; D002403:Cathepsins; C028217:cathepsin S