ArticleGenome biology2015
Graded gene expression changes determine phenotype severity in mouse models of CRX-associated retinopathies.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
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- Epigenetic-Mitochondrial-Metabolic Crosstalk in Retinal Pigment Epithelium (RPE) Dysfunction in Age-Related Macular Degeneration (AMD).Antioxidants (Basel, Switzerland) · 2026Review
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- Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominantGenome research · 2025Article
- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- Molecular basis of CRX/DNA recognition and stoichiometry at the Ret4 response element.Structure (London, England : 1993) · 2024Article
- Feline hypertrophic cardiomyopathy: Does the microRNA-mRNA regulatory network contribute to heart sarcomeric protein remodelling?International journal of experimental pathology · 2024Article
- Cone photoreceptor differentiation regulated by thyroid hormone transporter MCT8 in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathogenic variants inGenome research · 2024Article
- Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominantbioRxiv : the preprint server for biology · 2024Article
- Transcriptional precision in photoreceptor development and diseases - Lessons from 25 years of CRX research.Frontiers in cellular neuroscience · 2024Review
- Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.bioRxiv : the preprint server for biology · 2023Article
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- Active learning of enhancer and silencer regulatory grammar in photoreceptors.bioRxiv : the preprint server for biology · 2023Article
- Rho enhancers play unexpectedly minor roles in Rhodopsin transcription and rod cell integrity.Scientific reports · 2023Article
- Structural and functional analysis of the human cone-rod homeobox transcription factor.Proteins · 2022Article
- RNA Pol IV induces antagonistic parent-of-origin effects on Arabidopsis endosperm.PLoS biology · 2022Article
- Advancing human disease research with fish evolutionary mutant models.Trends in genetics : TIG · 2022Review
- Relationship between miR-203a inhibition and oil-induced toxicity in early life stage zebrafish (Toxicology reports · 2022Article
- Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection.BMC genomics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMutations 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.
resultsDespite 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 changes on the phenotype, as two mutants showed marginally distinguishable expression patterns but huge phenotypic differences, including distinct mechanisms of retinal degeneration.
conclusionsOur results implicate a threshold effect of gene expression level on photoreceptor function and survival, highlight the importance of CRX in photoreceptor subtype development and maintenance, and provide a molecular basis for phenotype variability in CRX-associated retinopathies.
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