000061812 001__ 61812
000061812 005__ 20171211083057.0
000061812 0247_ $$2doi$$a10.1186/1471-2164-15-59
000061812 0248_ $$2sideral$$a85259
000061812 037__ $$aART-2014-85259
000061812 041__ $$aeng
000061812 100__ $$0(orcid)0000-0003-3352-740X$$aFilali, H.
000061812 245__ $$aGene expression profiling of mesenteric lymph nodes from sheep with natural scrapie
000061812 260__ $$c2014
000061812 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061812 5203_ $$aBackground:
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.
000061812 536__ $$9info:eu-repo/grantAgreement/ES/MICINN-FEDER/AGL2008-0256
000061812 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061812 590__ $$a3.986$$b2014
000061812 591__ $$aGENETICS & HEREDITY$$b39 / 166 = 0.235$$c2014$$dQ1$$eT1
000061812 591__ $$aBIOTECHNOLOGY & APPLIED MICROBIOLOGY$$b26 / 163 = 0.16$$c2014$$dQ1$$eT1
000061812 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061812 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, I.$$uUniversidad de Zaragoza
000061812 700__ $$aHarders, F.
000061812 700__ $$0(orcid)0000-0001-6256-5478$$aVarona, L.$$uUniversidad de Zaragoza
000061812 700__ $$0(orcid)0000-0002-0827-110X$$aHedman, C.$$uUniversidad de Zaragoza
000061812 700__ $$0(orcid)0000-0002-8692-1382$$aMediano, D.R.
000061812 700__ $$0(orcid)0000-0002-2787-9671$$aMonzón, M.$$uUniversidad de Zaragoza
000061812 700__ $$aBossers, A.
000061812 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, J.J.$$uUniversidad de Zaragoza
000061812 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, R.$$uUniversidad de Zaragoza
000061812 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDepartamento de Patología Animal$$cSanidad Animal
000061812 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDepartamento de Anatomía, Embriología y Genética Animal$$cGenética
000061812 773__ $$g15, 59 (2014), 1-17$$pBMC genomics$$tBMC Genomics$$x1471-2164
000061812 8564_ $$s3369433$$uhttps://zaguan.unizar.es/record/61812/files/texto_completo.pdf$$yVersión publicada
000061812 8564_ $$s105298$$uhttps://zaguan.unizar.es/record/61812/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061812 909CO $$ooai:zaguan.unizar.es:61812$$particulos$$pdriver
000061812 951__ $$a2017-12-11-08:30:08
000061812 980__ $$aARTICLE