RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2 -deficient mice, a model for Rett syndrome

Molecular Autism
Natasha L PachecoMichelle L Olsen

Abstract

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. Much of our understanding of MeCP2 function is derived from transcriptomic studies with the general assumption that alterations in the transcriptome correlate with proteomic changes. Advances in mass spectrometry-based proteomics have facilitated recent interest in the examination of global protein expression to better understand the biology between transcriptional and translational regulation. We therefore performed the first comprehensive transcriptome-proteome comparison in a RTT mouse model to elucidate RTT pathophysiology, identify potential therapeutic targets, and further our understanding of MeCP2 function. The whole cortex of wild-type and symptomatic RTT male littermates (n = 4 per genotype) were analyzed using RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Ingenuity® Pathway Analysis was used to identify significantly affected pathways in the transcriptomic and proteomic data sets. Our results indicate these two "omics" data sets supplement one another. In addition to confirming previous works regarding mRNA expression in Mecp2-deficient animals, t...Continue Reading

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Apr 14, 2019·Brain and Behavior·Frank J SymonsWilliam R Kennedy
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Datasets Mentioned

BETA
GSE96684
PXD006460

Methods Mentioned

BETA
PCR
RNA-Seq
GTPase
protein folding
nucleotide exchange
deamination
acetylation
PLAA

Software Mentioned

Cufflinks Galaxy
Cuffmerge
Image Studio Lite
Ingenuity® Pathway Analysis ( IPA )
FastQC
TopHat Galaxy
Cuffdiff
SQLite
Origin2015
Trim Galore !

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