title: Gene expression profiling and association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.
abstract: The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.
authors.affiliation: Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Hicham
authors.initials: H
authors.lastname: Filali
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Martin-Burriel
authors.forename: Frank
authors.initials: F
authors.lastname: Harders
authors.forename: Luis
authors.initials: L
authors.lastname: Varona
authors.forename: Jaber
authors.initials: J
authors.lastname: Lyahyai
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badiola
authors.forename: Alex
authors.initials: A
authors.lastname: Bossers
authors.forename: Rosa
authors.initials: R
authors.lastname: Bolea
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011328:Prions / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology*; D012756:Sheep
chemical_list: D011328:Prions