Deletion mutants show that the 23-bp deletion in the upstream region of <i>PRNP</i> and/or the 12-bp deletion in intron1, coupled with the absence of the Sp1 SNP and the presence of exon1, are required for the negative feedback response to PrP overexpression during regulation of prion protein expression.
<p>(A) Deletion mutants of the DelDel constructs as shown on the left were used. Dotted box = Luciferase gene; black boxes = exon 1 and exon 2, which include numbers denoting the position of the reported transcription start site (+1) of the <i>PRNP</i> promoter region. The 23-bp indel, 12-bp indel, and SNP regions are also indicated above the reporter gene constructs. The absence (−) and presence (+) of each region in the reporter gene constructs are shown in the Table on the right. (B) Graph representing relative luciferase activities obtained with the above reporter plasmids in the presence of either an empty vector or pEF-boPrP. Relative luciferase activities (Mean ± S.D.) for 3 replicate experiments were compared with the pGL3-control plasmid (1%). A significant difference of luciferase activity in pEF-boPrP-transfected cells as compared with corresponding empty vector-transfected cells is shown by two asterisks (**, <0.01). NS indicates no significant difference.</p
