Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
PLoS One. 2011;6(5):e19909. doi: 10.1371/journal.pone.0019909. Epub 2011 May 24.
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.
天然瘙痒病和其他朊病毒病的发病机制仍不清楚。检查感染与对照动物的转录组变化可能会突出新的基因，这些基因可能参与朊病毒诱导的病理学的一些分子机制。本工作的目的是鉴定在天然瘙痒病呈症状期的绵羊尾髓（MO）中的基因表达谱中与疾病相关的改变。使用中央兽医研究所（CVI）定制的 4×44K 微阵列，比较了 7 只自然感染瘙痒病的绵羊的 MO 中的基因表达模式与 6 只对照的基因表达模式。微阵列由 CVI 先前对绵羊组织文库进行测序的探针组组成，并补充了所有目前公开的 Ovis aries 转录本。超过 350 个探针组的表达变化超过 2 倍。从这些探针中，我们鉴定了 148 个基因，其中许多基因编码参与免疫反应、离子转运、细胞粘附和转录的蛋白质。我们的结果证实了在诱导瘙痒病的鼠模型中观察到的先前发表的基因表达变化。此外，我们还鉴定了在瘙痒病中表现出差异表达的新基因，这些基因可能与朊病毒神经病理学有关。最后，我们研究了基因表达谱与主要瘙痒病相关病变（包括朊病毒蛋白沉积、神经胶质增生和海绵状变性）出现之间的关系。在这种情况下，讨论了 MO 中这些基因表达变化对瘙痒病发展的潜在影响。
