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Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing

Sevastou, I; Pryce, G; Baker, D; Selwood, DL; (2016) Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing. PLoS ONE , 11 (6) , Article e0157754. 10.1371/journal.pone.0157754. Green open access

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Abstract

Multiple sclerosis (MS) is a debilitating immune-mediated neurological disorder affecting young adults. MS is primarily relapsing-remitting, but neurodegeneration and disability accumulate from disease onset. The most commonly used mouse MS models exhibit a monophasic immune response with fast accumulation of neurological damage that does not allow the study of progressive neurodegeneration. The chronic relapsing and secondary progressive EAE (pEAE) Biozzi ABH mouse model of MS exhibits a reproducible relapsing-remitting disease course that slowly accumulates permanent neurological deficit and develops a post-relapsing progressive disease that permits the study of demyelination and neurodegeneration. RNA sequencing (RNAseq) was used to explore global gene expression in the pEAE Biozzi ABH mouse. Spinal cord tissue RNA from pEAE Biozzi ABH mice and healthy age-matched controls was sequenced. 2,072 genes were differentially expressed (q<0.05) from which 1,397 were significantly upregulated and 675 were significantly downregulated. This hypothesis-free investigation characterised the genomic changes that describe the pEAE mouse model. The differentially expressed genes revealed a persistent immunoreactant phenotype, combined with downregulation of the cholesterol biosynthesis superpathway and the LXR/RXR activation pathway. Genes differentially expressed include the myelination genes Slc17a7, Ugt8A and Opalin, the neuroprotective genes Sprr1A, Osm and Wisp2, as well as genes identified as MS risk factors, including RGs14 and Scap2. Novel genes with unestablished roles in EAE or MS were also identified. The identification of differentially expressed novel genes and genes involved in MS pathology, opens the door to their functional study in the pEAE mouse model which recapitulates some of the important clinical features of progressive MS.

Type: Article
Title: Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0157754
Publisher version: http://doi.org/10.1371/journal.pone.0157754
Language: English
Additional information: Copyright: © 2016 Sevastou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CENTRAL-NERVOUS-SYSTEM, EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, INHIBIT INFLAMMATORY RESPONSES, MULTIPLE-SCLEROSIS PATIENTS, ACTIVATED-RECEPTOR-ALPHA, REPEAT PROTEIN 1A, LIVER X RECEPTORS, LIPID-METABOLISM, MATRIX METALLOPROTEINASE-12, ALZHEIMERS-DISEASE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
UCL > Provost and Vice Provost Offices > VP: Health
UCL > Provost and Vice Provost Offices > VP: Health > Translational Research Office
URI: https://discovery.ucl.ac.uk/id/eprint/1518950
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