title: Identification of polymorphisms in the ovine Shadow of prion protein (SPRN) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie.
abstract: Shadow of prion protein (SPRN) is an interesting candidate gene thought to be involved in prion pathogenesis. In humans, an association has already been discovered between mutations in SPRN and the incidence of variant and sporadic Creutzfeldt-Jakob disease. However, in sheep, the effect of mutations in SPRN is largely unknown. Therefore, we analysed the presence of mutations in the entire ovine SPRN gene, their association with scrapie susceptibility and their effect on SPRN promoter activity. In total, 26 mutations were found: seven in the promoter region, four in intron 1, seven in the coding sequence and eight in the 3' untranslated region. The mutations detected in the coding sequence and the promoter region were subsequently analysed in more detail. In the coding sequence, a polymorphism causing a deletion of two alanines was found to be associated with susceptibility for classical scrapie in sheep. Furthermore, a functional analysis of deletion constructs of the ovine SPRN promoter revealed that the region 464 to 230 bp upstream of exon 1 (containing a putative AP-2 and putative Sp1 binding sites) is of functional importance for SPRN transcription. Six mutations in the SPRN promoter were also found to alter the promoter activity in vitro. However, no association between any of these promoter mutations and susceptibility for classical scrapie was found.
authors.affiliation: Department of Nutrition, Genetics and Ethology, Ghent University, Merelbeke, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Lampo
authors.forename: L
authors.initials: L
authors.lastname: Duchateau
authors.forename: B
authors.initials: B
authors.lastname: Schepens
authors.forename: M
authors.initials: M
authors.lastname: Van Poucke
authors.forename: X
authors.initials: X
authors.lastname: Saelens
authors.forename: T
authors.initials: T
authors.lastname: Erkens
authors.forename: A
authors.initials: A
authors.lastname: Van Zeveren
authors.forename: L J
authors.initials: LJ
authors.lastname: Peelman
mesh_terms: D000818:Animals; D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012608:Scrapie / Q000235:genetics*; D012756:Sheep / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins