ArticleThe Journal of clinical investigation2014
OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 86 citations in OpenAlex.
- Cone Rod Homeobox (Ophthalmic genetics · 2025Review
- Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominantGenome research · 2025Article
- Molecular basis of CRX/DNA recognition and stoichiometry at the Ret4 response element.Structure (London, England : 1993) · 2024Article
- Retinal primary cilia and their dysfunction in retinal neurodegenerative diseases: beyond ciliopathies.Molecular medicine (Cambridge, Mass.) · 2024Review
- 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
- CRX haploinsufficiency compromises photoreceptor precursor translocation and differentiation in human retinal organoids.Stem cell research & therapy · 2023Article
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- Progenitor division and cell autonomous neurosecretion are required for rod photoreceptor sublaminar positioning.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cat LCA-CRX Model, Homozygous for an Antimorphic Mutation Has a Unique Phenotype.Translational vision science & technology · 2023Article
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Gene Augmentation for Autosomal Dominant CRX-Associated Retinopathies.Advances in experimental medicine and biology · 2023Review
- Blimp-1/PRDM1 and Hr3/RORβ specify the blue-sensitive photoreceptor subtype inFrontiers in cell and developmental biology · 2023Article
- Developmental genome-wide occupancy analysis of bZIP transcription factor NRL uncovers the role of c-Jun in early differentiation of rod photoreceptors in the mammalian retina.Human molecular genetics · 2022Article
- Mutations inScience advances · 2022Article
- Article
- Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?International journal of molecular sciences · 2021Review
- Gene Therapy of Dominant CRX-Leber Congenital Amaurosis using Patient Stem Cell-Derived Retinal Organoids.Stem cell reports · 2021Article
- Loss of endocytosis-associated RabGEF1 causes aberrant morphogenesis and altered autophagy in photoreceptors leading to retinal degeneration.PLoS genetics · 2020Article
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Leber congenital amaurosis (LCA) encompasses a set of early-onset blinding diseases that are characterized by vision loss, involuntary eye movement, and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA, which is typically recessive; however, mutations in homeodomain transcription factor CRX lead to an autosomal dominant form of LCA. The mechanism of CRX-associated LCA is not understood. Here, we identified a spontaneous mouse mutant with a frameshift mutation in Crx (CrxRip). We determined that CrxRip is a dominant mutation that results in congenital blindness with nonrecordable response by ERG and arrested photoreceptor differentiation with no associated degeneration. Expression of LCA-associated dominant CRX frameshift mutations in mouse retina mimicked the CrxRip phenotype, which was rescued by overexpression of WT CRX. Whole-transcriptome profiling using deep RNA sequencing revealed progressive and complete loss of rod differentiation factor NRL in CrxRip retinas. Expression of NRL partially restored rod development in CrxRip/+ mice. We show that the binding of homeobox transcription factor OTX2 at the Nrl promoter was obliterated in CrxRip mice and ectopic expression of OTX2 rescued the rod differentiation defect. Together, our data indicate that OTX2 maintains Nrl expression in developing rods to consolidate rod fate. Our studies provide insights into CRX mutation-associated congenital blindness and should assist in therapeutic design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.