Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse wild type and Abcd1 -/- spinal cord over time to study X-Adrenoleukodystrophy (X-Ald) disease progression

ABSTRACT: X-Adrenoleukodystrophy (X-Ald) disease progression was studied by comparing expression patterns of Abcd1 -/- mouse spinal cords from 3.5, 12 and 22 months of age compared to healthy littermates spinal cords at the same time points.

ORGANISM(S): Mus musculus

SUBMITTER: Aurora Pujol

PROVIDER: E-MTAB-79 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy.

Schlüter Agatha A Espinosa Lluís L Fourcade Stéphane S Galino Jorge J López Eva E Ilieva Ekaterina E Morató Laia L Asheuer Muriel M Cook Ted T McLaren Alistair A Reid Juliet J Kelly Fiona F Bates Stewart S Aubourg Patrick P Galea Elena E Pujol Aurora A

Human molecular genetics 20111117 5

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of ve ...[more]

PMID: 22095690

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Project description:X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms. How same mutation in the ABCD1 gene can lead to clinically very distinct phenotypes and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. We wonder whether epigenetics mechanisms could answer the lack of genotype-phenotype correlation. We employed Illumina state of the art technology to analyze the differential methylation of over 485,000 CpG sites throughout the entire human genome and used stringent statistical criteria to define differential methylation patterns between brains of cALD, cAMN and age-matched controls. We identified a common X-ALD methylation signature comprising the hypermethylation in genes harboring the trimethylated histone H3K27me3 mark in their promoters, the hypermethylation for genes driven the oligodendrocyte lineage, and the hypomethylation for immune-associated genes. We also examined the methylated differences between cALD and cAMN resulting with differential immune response pathways and concordance methylation levels with phenotype severity. The detected methylation differences correlated with transcriptional and translational consequences, as supported by Affymetrix expression arrays, quantitative PCR and WB changes. The reliability of these changes was further demonstrated by validating DNA methylation by an independent pyrosequencing assay. From these evidences, we propose the altered transcriptional programs in oligodendrocyte differentiation in X-ALD patients. These observations may provide new therapeutic epigenetic agents.

Dataset Information

Transcription profiling of mouse wild type and Abcd1 -/- spinal cord over time to study X-Adrenoleukodystrophy (X-Ald) disease progression

Publications

Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy.

Similar Datasets

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