NR ABCI
AU Baybutt,H.N.; Manson,J.
TI Characterisation of two promoters for prion protein (PrP) gene expression in neuronal cells
QU Gene 1997 Jan 3; 184(1): 125-31
PT journal article
AB The neuronal membrane protein, PrP, has a key role in the development of the transmissible spongiform encephalopathies and the level of expression of the PrP gene has been shown to affect the disease profile. In order to define the sequences that are responsible for the normal expression of the PrP gene we have isolated and sequenced a 5' region of the murine PrP gene, which includes 1.2 kb upstream from exon 1, intron I and exon 2. Sequencing of this region from several strains of mice identified a polymorphism linked to Sinc, the gene controlling the incubation period of scrapie in mice. We used this gene fragment and deletions of it to examine promoter mediated expression of a cat (chloramphenicol acetyl transferase) reporter gene in neuroblastoma cells (N2a). Both promoter and suppressor elements were identified within this region. The two major areas of promoter activity were sequences adjacent to and 5' to exons 1 and 2. The 5' region of intron 1 was shown to contain elements that were capable of suppressing promoter activity. Transcription factor binding sites have been identified within these sequences.
IN Die Autoren isolierten und sequenzierten eine 5'Region des Prionproteins von verschiedenen Mäusestämmen und identifizierten einen Polymorphismus, der mit dem Sinc-Genotyp verbunden zu sein scheint. Mit Deletionsstudien an einem Fusionsgen aus dem Prionpromoter vor dem CAT-Gen wurden in der 5'Region Promoter- und Suppressor-Elemente identifiziert. In der 5'Region des ersten Introns des Priongenes wurden Elemente gefunden, welche die Promotion unterdrücken.
MH Animal; Base Sequence; Binding Sites/genetics; Chloramphenicol O-Acetyltransferase/genetics/metabolism; Cloning, Molecular; Gene Expression Regulation/*genetics; Genes, Reporter/genetics; Mice; Molecular Sequence Data; Neuroblastoma; Polymorphism (Genetics)/genetics; Pregnancy Proteins/chemistry/*genetics; Promoter Regions (Genetics)/*genetics; Scrapie/genetics/metabolism; Sequence Analysis; Sequence Deletion/genetics; Transcription Factors/genetics/metabolism; Transfection/genetics; Tumor Cells, Cultured
AD Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Edinburgh, UK. herbert.Baybutt@bbsrc.ac.uk
SP englisch
PO Niederlande