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Open Access Research article

Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie

Hicham Filali1, Inmaculada Martín-Burriel2, Frank Harders3, Luis Varona4, Carlos Hedman1, Diego R Mediano2, Marta Monzón1, Alex Bossers3, Juan J Badiola1 and Rosa Bolea1*

Author Affiliations

1 Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain

2 Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain

3 Central Veterinary Institute part of Wageningen UR (CVI), Lelystad, The Netherlands

4 Unidad de Genética Cuantitativa y Mejora Animal, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain

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BMC Genomics 2014, 15:59  doi:10.1186/1471-2164-15-59

Published: 23 January 2014

Abstract

Background

Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease.

Results

In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR.

Conclusions

The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.

Keywords:
Natural scrapie; Mesenteric lymph node; Microarray; Gene expression; Real time PCR; Prion