Graded gene expression changes determine phenotype severity in mouse models of CRX-associated retinopathies

Genome Biology
Philip A RuzyckiShiming Chen

Abstract

Mutations in the cone-rod-homeobox protein CRX are typically associated with dominant blinding retinopathies with variable age of onset and severity. Five well-characterized mouse models carrying different Crx mutations show a wide range of disease phenotypes. To determine if the phenotype variability correlates with distinct changes in CRX target gene expression, we perform RNA-seq analyses on three of these models and compare the results with published data. Despite dramatic phenotypic differences between the three models tested, graded expression changes in shared sets of genes are detected. Phenotype severity correlates with the down-regulation of genes encoding key rod and cone phototransduction proteins. Interestingly, in increasingly severe mouse models, the transcription of many rod-enriched genes decreases decrementally, whereas that of cone-enriched genes increases incrementally. Unlike down-regulated genes, which show a high degree of CRX binding and dynamic epigenetic profiles in normal retinas, the up-regulated cone-enriched genes do not correlate with direct activity of CRX, but instead likely reflect a change in rod cell-fate integrity. Furthermore, these analyses describe the impact of minor gene expression chan...Continue Reading

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Jun 20, 2017·Current Biology : CB·Chloe PotterDidier Hodzic
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Datasets Mentioned

BETA
GSE65506

Methods Mentioned

BETA
RNA-seq
PCA
PCR
ChIP-seq
immunoprecipitation
RIP
genotyping
Illumina sequencing
RNAseq
RNA seq

Software Mentioned

TopHat
EdgeR
BEDTools
Samtools
HOMER
Integrated Genomics Viewer ( IGV )
stats R package
MacVector
IGV
HTSeq package

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