Affinage

CRB1

Protein crumbs homolog 1 · UniProt P82279

Length
1406 aa
Mass
154.2 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRB1 is a transmembrane polarity determinant that organizes an apical protein scaffold at the outer limiting membrane of the retina and at epithelial junctional complexes in the colon, maintaining adherens junction integrity and controlling progenitor cell proliferation. At the subapical region adjacent to adherens junctions, CRB1 recruits PALS1/MPP5 and MPP4 into a conserved Crumbs complex that stabilizes the spectrin cytoskeleton, regulates RAB11A-dependent endosomal recycling of NOTCH1, and restrains Notch1/YAP-Hippo signaling in retinal progenitor cells; compound loss of CRB1 and its paralog CRB2 converts retinitis pigmentosa–like pathology to Leber congenital amaurosis through progenitor cell dysregulation before E12.5 (PMID:24339791, PMID:31145883, PMID:37541258). CRB1 also maintains colonic epithelial barrier function, and its loss permits intestinal bacterial translocation to the retina, driving secondary retinal degeneration that can be rescued by restoring CRB1 expression in colonic epithelium alone (PMID:38412859). Loss-of-function mutations in CRB1 cause retinitis pigmentosa type 12 and Leber congenital amaurosis type 8 (PMID:10508521, PMID:24565864).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Identification of CRB1 as a Crumbs homolog with a large extracellular domain architecture (19 EGF-like, 3 laminin A G-like, C-type lectin domains) established that a conserved polarity determinant operates in the human retina and that its disruption causes RP12.

    Evidence cDNA cloning, suppression subtractive hybridization, and mutation screening in RP12 families

    PMID:10508521

    Open questions at the time
    • No protein localization data in mammalian retina yet obtained
    • Functional mechanism entirely inferred from Drosophila Crumbs analogy
  2. 2001 High

    Demonstrating that the CRB1 cytoplasmic domain can functionally replace Drosophila Crumbs in rescue experiments established that CRB1 organizes an intracellular protein scaffold through its conserved FERM-binding and PDZ-binding motifs.

    Evidence Alternative splice variant cloning and Drosophila rescue/overexpression assays

    PMID:11734541

    Open questions at the time
    • Identity of mammalian scaffold partners unknown
    • Whether extracellular domain contributes to function not tested
  3. 2002 High

    Localization of Crumbs/CRB1 to the photoreceptor apical membrane and demonstration that it stabilizes zonula adherens and the spectrin cytoskeleton during rhabdomere morphogenesis revealed a polarity-independent structural role at adherens junctions.

    Evidence Loss-of-function genetics in Drosophila with immunolocalization and live imaging of rhabdomere development

    PMID:11850625

    Open questions at the time
    • Mammalian spectrin-CRB1 link not directly tested
    • Mechanism of cytoskeletal stabilization unclear
  4. 2003 High

    The rd8 mouse model proved that CRB1 is essential for outer limiting membrane integrity in mammals: its loss fragments adherens junctions between Müller glia and photoreceptors, causing shortened segments and pseudorosettes from early postnatal ages.

    Evidence Histopathology, immunostaining for adherens junction proteins, and funduscopy in rd8 mice; OCT imaging in human CRB1 patients showing thickened, poorly laminated retinas

    PMID:12700176 PMID:12915475

    Open questions at the time
    • Relative contribution of Müller glia vs. photoreceptors to phenotype unknown
    • Downstream signaling pathways not identified
  5. 2005 High

    Identification of MPP4 as a novel CRB1 scaffold member recruited via MPP5/PALS1 defined the molecular composition of the mammalian Crumbs complex at the OLM.

    Evidence Yeast two-hybrid, reciprocal Co-IP, GST pulldown, immunoelectron microscopy at the OLM

    PMID:15914641

    Open questions at the time
    • Functional consequence of MPP4 loss for OLM integrity not tested
    • Whether additional MAGUK proteins participate unknown
  6. 2006 High

    RNAi knockdown of PALS1/MPP5 demonstrated it is required for CRB1 localization to the subapical region in Müller glia, and immuno-EM confirmed CRB1 predominates in Müller glial cells at the SAR, establishing a cell-type hierarchy in the Crumbs complex.

    Evidence RNA interference in primary retinal Müller glia cultures, immunoelectron microscopy in mouse retina

    PMID:16885194

    Open questions at the time
    • Whether CRB1 in photoreceptors is independently targeted or also PALS1-dependent
    • No live-cell trafficking data
  7. 2007 Medium

    A C249W knock-in showed that extracellular domain missense mutations can allow normal CRB1 trafficking to the SAR, while loss of CRB1 deregulates Pttg1 expression and alters Müller glial apical villi, broadening the known cellular consequences of CRB1 loss.

    Evidence Knock-in mouse, scanning laser ophthalmoscopy, gene expression analysis; separate study in Crb1−/− mice analyzing Müller glia apical villi

    PMID:17234588 PMID:17705196

    Open questions at the time
    • Mechanism linking CRB1 loss to Pttg1 deregulation unknown
    • Whether apical villi defects are cell-autonomous not resolved
  8. 2012 High

    Conditional ablation of CRB2 phenocopied CRB1-associated RP, including increased late-born progenitor proliferation, establishing that CRB1 and CRB2 function redundantly to restrain retinal progenitor cell expansion.

    Evidence Conditional CRB2 knockout in developing retina with electroretinography, histology, and immunostaining

    PMID:23001562

    Open questions at the time
    • Signaling pathway mediating proliferation control not identified at this point
    • Quantitative contribution of each paralog uncertain
  9. 2013 High

    Double knockout of CRB1/CRB2 in retinal progenitors revealed that the Crumbs complex restrains proliferation via Notch1 and YAP/Hippo pathway regulation, with increased P120-catenin, explaining the thickened retinal phenotype of LCA8 patients.

    Evidence Conditional double knockout mice with flow cytometry (cell cycle), gene expression for Notch1 and YAP targets, immunostaining

    PMID:24339791

    Open questions at the time
    • Direct biochemical link between CRB1 and Notch1/YAP pathway components not shown
    • Whether P120-catenin increase is cause or consequence unclear
  10. 2014 High

    Genetic epistasis between Crb1 and Crb2 alleles, combined with species-specific expression mapping showing CRB1 in both photoreceptors and Müller glia of human retina (unlike mouse), explained the variable severity of CRB1 mutations producing RP versus LCA.

    Evidence Compound Crb1/Crb2 mutant mice with graded allelic combinations, immunohistochemistry in human retina

    PMID:24565864

    Open questions at the time
    • Modifier genes beyond CRB2 not systematically tested
    • Mechanism of species-specific promoter regulation unknown
  11. 2019 High

    Conditional deletion at different developmental stages demonstrated that CRB1/CRB2 loss from the optic vesicle stage causes LCA-like defects arising before E12.5 in progenitor cells, while loss restricted to Müller glia converts RP-like to LCA-like pathology, establishing cell-type and timing determinants of disease severity.

    Evidence Multiple conditional double KO strategies (mRx-Cre, Müller glia-specific Cre), electroretinography, histological analysis; ultrastructural localization in non-human primates

    PMID:30239717 PMID:31145883

    Open questions at the time
    • Precise progenitor cell subtype affected not identified
    • No rescue experiment at the optic vesicle stage
  12. 2023 High

    CRB1 was shown to regulate endosomal recycling: patient organoids lacking CRB1 have fewer RAB11A+ recycling endosomes, decreased VPS35, and more degradative compartments, while proximity ligation assays demonstrated CRB1–NOTCH1 extracellular interaction, linking CRB1 directly to Notch recycling and signaling.

    Evidence hiPSC-derived retinal organoids (patient vs. isogenic controls), proximity ligation assay, immunostaining for endosomal markers, scRNA-seq

    PMID:37541258

    Open questions at the time
    • Whether CRB1–NOTCH1 interaction is direct or bridged not resolved biochemically
    • Retromer/VPS35 connection not confirmed by rescue experiment
  13. 2024 High

    Discovery that CRB1 maintains colonic epithelial barrier function and that Rd8-associated retinal degeneration is driven by bacterial translocation from the gut — rescuable by colonic CRB1 re-expression — revealed an unexpected extra-retinal mechanism of disease pathogenesis.

    Evidence Rd8 mouse model with bacterial depletion and tissue-specific CRB1 gene delivery to colonic epithelium, barrier assays, retinal lesion scoring

    PMID:38412859

    Open questions at the time
    • Which bacterial species or products drive retinal inflammation not identified
    • Whether human CRB1 patients have intestinal barrier defects not tested
    • Mechanism by which CRB1 maintains colonic tight junctions not elucidated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CRB1 extracellular domain interactions (with NOTCH1 and in trans adhesion), the precise mechanism linking CRB1 loss to RAB11A/VPS35-dependent recycling defects, whether intestinal barrier dysfunction contributes to retinal disease in human CRB1 patients, and what additional modifier loci beyond CRB2 determine RP-vs-LCA clinical outcome.
  • No high-resolution structure of CRB1 extracellular domain
  • Biochemical reconstitution of CRB1-dependent endosomal recycling not performed
  • Human gut barrier phenotype in CRB1 patients untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 7 GO:0005576 extracellular region 1 GO:0005768 endosome 1
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
CRB2MPP4MPP5NOTCH1RAB11ATJP1VPS35
Complex memberships
Crumbs complex (CRB1-PALS1/MPP5-MPP4)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CRB1 encodes a protein with 19 EGF-like domains, 3 laminin A G-like domains, and a C-type lectin domain, homologous to Drosophila Crumbs, suggesting a role in cell-cell interaction and maintenance of cell polarity in the retina. Mutations disrupting the ORF cause retinitis pigmentosa (RP12). cDNA cloning, suppression subtractive hybridization, sequencing of patient mutations Nature genetics High 10508521
2001 An alternative splice variant of human CRB1 encodes a cytoplasmic domain 72% similar to Drosophila Crumbs, with two intracellular subdomains necessary for function absolutely conserved. Rescuing and overexpression studies in Drosophila showed that the cytoplasmic domains are functionally interchangeable between species, suggesting CRB1 organizes an intracellular protein scaffold in the human retina. Alternative splice variant cloning, Drosophila rescue and overexpression assays Human molecular genetics High 11734541
2002 Drosophila Crumbs (CRB1 ortholog) and mammalian CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane (stalk in Drosophila; inner segment in mammals). Crumbs is required to maintain zonula adherens integrity during rhabdomere morphogenesis and stabilizes the membrane-associated spectrin cytoskeleton, a function distinct from its role in epithelial apical-basal polarity. Loss-of-function genetics in Drosophila, immunolocalization, live imaging, phenotypic analysis of rhabdomere and stalk development Nature High 11850625
2003 CRB1 is essential for external limiting membrane (ELM) integrity in the mammalian retina. Loss of CRB1 (rd8 frameshift mutation truncating transmembrane and cytoplasmic domains) causes discontinuous/fragmented adherens junction staining at the ELM, shortened photoreceptor inner and outer segments from 2 weeks of age, and retinal folds/pseudorosettes, indicating a developmental defect in photoreceptor morphogenesis. Mouse knockout (rd8 model), histopathology, immunostaining for adherens junction proteins, funduscopy Human molecular genetics High 12915475
2003 CRB1 mutations in humans result in retinas that are abnormally thick with lack of distinct layering, resembling immature retina, suggesting CRB1 disrupts development of normal retinal organization by interrupting naturally occurring apoptosis. In vivo high-resolution retinal cross-section imaging (OCT) in patients with CRB1 mutations Human molecular genetics Medium 12700176
2005 MPP4 (a MAGUK protein) is a novel member of the CRB1 scaffold complex, recruited to the complex through direct interaction with MPP5 (PALS1). CRB1, MPP5, and MPP4 colocalize at the outer limiting membrane (OLM) in the retina. 3D homology modeling provided a mechanism for homo- and heterodimer recruitment of MPP4 and MPP5 to the complex. Yeast two-hybrid screening, GST pulldown, co-immunoprecipitation, immunohistochemistry, immunoelectron microscopy, 3D homology modeling Investigative ophthalmology & visual science High 15914641
2006 Pals1 (MPP5) is required for correct localization of CRB1 at the subapical region (SAR) in polarized Müller glial cells. RNAi-mediated silencing of Pals1 in Müller cells results in loss of CRB1, CRB2, MUPP1, and Veli3 protein localization and partial loss of CRB3. CRB1 immunoreactivity by immuno-EM is predominantly at the SAR in Müller glial cells. Immunoelectron microscopy, RNA interference, immunohistochemistry, primary retinal cultures from Crb1-/- mice Human molecular genetics High 16885194
2007 A Cys249Trp knock-in mutation in the extracellular sixth calcium-binding EGF domain of Crb1 allows normal trafficking of the mutant protein to the subapical region adjacent to adherens junctions at the OLM, demonstrating that missense mutations in the extracellular domain do not necessarily prevent protein localization. Loss of Crb1 (C249W or knockout) deregulates expression of Pttg1 (pituitary tumor transforming gene 1) in the retina. Knock-in mouse generation, scanning laser ophthalmoscopy, gene expression analysis, immunohistochemistry The Journal of neuroscience Medium 17234588
2007 Loss of Crb1 in Müller glial cells results in an irregular number and size of apical villi, demonstrating that Crb1 is required to regulate number and size of Müller glia cell apical villi; subsequent loss of retinal integrity leads to neovascularization. Crb1-/- mouse analysis, aging and light exposure studies, immunohistochemistry, confocal microscopy Glia Medium 17705196
2010 CRB1 protein at the outer limiting membrane (OLM) forms adherens junctions between Müller glia and photoreceptors. Disruption of CRB1 (in Crb1rd8/rd8 mice) or siRNA knockdown of the CRB1-interacting protein ZO-1 disrupts OLM integrity, significantly increasing integration of transplanted photoreceptor precursors into the retina. Photoreceptor transplantation in Crb1rd8/rd8 mice, siRNA knockdown of ZO-1, cell counting of integrated donor cells Cell transplantation Medium 20089206
2012 Loss of CRB2 in the developing retina causes progressive disorganization, abnormal lamination of immature rod photoreceptors, disruption of adherens junctions between photoreceptors and Müller glia, increased number of late-born progenitor cells and rod photoreceptors, and programmed cell death of rod photoreceptors—mimicking human retinitis pigmentosa due to CRB1 mutations. This reveals an essential role for the CRB2 paralog in photoreceptor layer lamination and suppression of late progenitor proliferation. Conditional knockout mouse (CRB2 ablation in developing retina), confocal scanning laser ophthalmoscopy, SD-OCT, electroretinography, histological analysis, immunostaining Human molecular genetics High 23001562
2013 Ablation of both Crb1 and Crb2 in retinal progenitor cells causes severe retinal dysfunction, abnormal lamination, and retinal thickening mimicking Leber congenital amaurosis. CRB1 and CRB2 restrain proliferation of retinal progenitor cells; their loss results in altered cell cycle progression, increased mitotic cells, and increased late-born cell types. Mechanistically, loss of CRB1/CRB2 dysregulates Notch1 and YAP/Hippo signaling pathway target genes and increases P120-catenin levels. Conditional double knockout mice, electroretinography, flow cytometry (cell cycle analysis), immunostaining, gene expression analysis for Notch1 and YAP/Hippo targets PLoS genetics High 24339791
2014 CRB2 acts as a modifying gene of CRB1-related retinal dystrophies in mice. In human retina (unlike mouse), CRB1 protein is expressed at the subapical region in both photoreceptors and Müller glia cells, while CRB2 is expressed only in Müller glia cells. Genetic ablation of one Crb2 allele in Crb1 knockout mice leads to earlier and more severe retinal phenotype, providing mechanistic insight for the variable CRB1-related LCA vs. RP phenotypes. Genetic epistasis (Crb1/Crb2 compound mutant mice), immunohistochemistry, OCT, electroretinography, human retinal immunostaining Human molecular genetics High 24565864
2015 AAV-mediated CRB2 gene therapy targeting both Müller glial cells and photoreceptors ameliorates retinal function and structure in Crb1 mouse models. Targeting only a single cell type or using CRB1 vectors reduced retinal function, demonstrating that CRB expression in both Müller glia and photoreceptors is required for functional rescue. AAV gene therapy in Crb1 mouse models, electroretinography, retinal morphology analysis Human molecular genetics Medium 25701872
2015 A spontaneous CRB1 indel mutation in Brown Norway rats (BN-J) causes dislocation of CRB1 protein from the retinal Müller glia/photoreceptor junction. Transcriptomic analysis identified dysregulated pathways including TGF-β, MAPK cascade, growth factor/inflammatory pathways, G-protein signaling, actin cytoskeleton regulation, and cardiovascular signaling in Müller glial cells, linking CRB1 loss in Müller glia to retinal telangiectasia. Genetic analysis, immunohistochemistry, primary RMG cultures, transcriptomics The Journal of neuroscience Medium 25878282
2019 Human CRB1 and CRB2 proteins localize to the subapical region in photoreceptors and Müller glial cells of human fetal retina, with CRB2 expression preceding CRB1 during development. This fetal CRB complex formation is recapitulated in hiPSC-derived retinal organoids. CRB1 patient iPSC retinal organoids show disruptions at the outer limiting membrane consistent with Crb1 mutant mouse phenotypes. hiPSC-derived retinal organoids, immunohistochemistry in human fetal and organoid retina, comparison with Crb1 mutant mice Stem cell reports Medium 30956116
2019 Loss of both CRB1 and CRB2 specifically in Müller glial cells converts a CRB1-associated RP-like retinal phenotype into an LCA-like phenotype. CRB1 and CRB2 proteins in non-human primate retinas localize to the subapical region adjacent to adherens junctions at the OLM in both Müller glial cells and photoreceptors, as confirmed by ultrastructural immunolocalization. Conditional double knockout mice (CRB1/CRB2 in Müller glia), electroretinography, immunoelectron microscopy in non-human primates Human molecular genetics High 30239717
2019 Targeted deletion of Crb1 and Crb2 from the optic vesicle stage causes locally thickened retina with spots devoid of cells, aberrant retinal cell positioning, severely disrupted lamination, depigmented RPE, and severely attenuated electroretinogram—modeling human LCA8. Retinal defects arise before E12.5, indicating LCA8 is caused by malfunction of retinal progenitor cells during early ocular development rather than defective photoreceptor-Müller glial interaction. Conditional double knockout (mRx-Cre driver), electroretinography, histological analysis, cell positioning analysis Developmental biology High 31145883
2023 CRB1 is required for recycling via RAB11A+ vesicles in human retinal organoids. CRB1 patient organoids show decreased CRB1 and NOTCH1 expression at the outer limiting membrane, increased WDFY1+ vesicles, fewer RAB11A+ recycling endosomes, decreased VPS35 retromer complex components, and more degradative endolysosomal compartments. Proximity ligation assays demonstrate that human CRB1 and NOTCH1 can interact via their extracellular domains. hiPSC-derived retinal organoids from CRB1 patients vs. isogenic controls, proximity ligation assay, immunostaining for endosomal markers, scRNA-seq Stem cell reports High 37541258
2024 Normal CRB1 expression is enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes. Rd8 mutations in Crb1 impair the outer blood-retinal barrier and colonic intestinal epithelial barrier, enabling translocation of intestinal bacteria from the GI tract to the retina. Depletion of bacteria systemically or reintroduction of normal Crb1 expression specifically in colonic epithelium rescued Rd8-associated retinal degeneration without reversing the retinal barrier breach, establishing that CRB1 maintains barrier function at both retinal and intestinal epithelial sites. Rd8 mouse model, bacterial depletion experiments, colonic CRB1 re-expression (gene delivery), retinal lesion scoring, barrier function assays Cell High 38412859
2004 A novel secretory isoform of mouse Crb1 (Crb1s), generated by retention of the 3' end of exon 6, lacks transmembrane and cytoplasmic domains and is secreted. Unlike canonical Crb1 (restricted to brain and eye), Crb1s is expressed in various tissues including skin, lung, and kidney. In keratinocytes, Crb1s is secreted as an ~80 kDa form and after Ca2+-induced differentiation associates with focal adhesions and cell-cell contacts. Cloning of alternative splice variant, RT-PCR expression analysis, immunolocalization in skin/keratinocytes, Ca2+-induced differentiation assay Biochemical and biophysical research communications Medium 14684155
2007 Overexpression of human CRB1, CRB2, or CRB3 in mammalian cells does not result in direct interaction with presenilin complex components and does not alter levels of presenilin complex components, NCT maturation, PS endoproteolysis, or Aβ/AICD/NICD production, indicating CRB1 is not a significant direct modulator of presenilin-dependent γ/ε-secretase activity in mammalian cells. Co-immunoprecipitation, overexpression in cultured mammalian cells, Western blotting for gamma-secretase activity readouts Biochemistry Medium 17988153

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Investigative ophthalmology & visual science 591 22447858
1999 Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). Nature genetics 398 10508521
2002 Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature 356 11850625
2003 CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Human molecular genetics 320 12915475
2001 Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. American journal of human genetics 285 11389483
2003 Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Human molecular genetics 199 12700176
2001 Mutations in the CRB1 gene cause Leber congenital amaurosis. Archives of ophthalmology (Chicago, Ill. : 1960) 199 11231775
2011 CRB1 mutations in inherited retinal dystrophies. Human mutation 165 22065545
2004 CRB1 mutation spectrum in inherited retinal dystrophies. Human mutation 155 15459956
2010 Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1. The British journal of ophthalmology 99 20956273
2002 Isolation of Crb1, a mouse homologue of Drosophila crumbs, and analysis of its expression pattern in eye and brain. Mechanisms of development 99 11744384
2010 Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina. Cell transplantation 98 20089206
2006 Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Muller glia cells. Human molecular genetics 90 16885194
2014 The CRB1 and adherens junction complex proteins in retinal development and maintenance. Progress in retinal and eye research 87 24508727
2005 Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene. Investigative ophthalmology & visual science 86 15623792
2017 Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study. Ophthalmology 79 28341475
2019 Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5. Stem cell reports 78 30956116
2005 Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Journal of medical genetics 76 16272259
2012 Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene. Human molecular genetics 71 23001562
2007 A single amino acid substitution (Cys249Trp) in Crb1 causes retinal degeneration and deregulates expression of pituitary tumor transforming gene Pttg1. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 17234588
2015 Gene therapy into photoreceptors and Müller glial cells restores retinal structure and function in CRB1 retinitis pigmentosa mouse models. Human molecular genetics 69 25701872
2001 CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila. Human molecular genetics 67 11734541
2007 Crb1 is a determinant of retinal apical Müller glia cell features. Glia 66 17705196
2013 High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population. Orphanet journal of rare diseases 64 23379534
2013 Targeted ablation of CRB1 and CRB2 in retinal progenitor cells mimics Leber congenital amaurosis. PLoS genetics 64 24339791
2014 Whole exome sequencing identifies CRB1 defect in an unusual maculopathy phenotype. Ophthalmology 60 24811962
2005 MPP5 recruits MPP4 to the CRB1 complex in photoreceptors. Investigative ophthalmology & visual science 59 15914641
1994 Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population. Genomics 59 8001962
2019 Mechanisms of Cr(VI) reduction by Bacillus sp. CRB-1, a novel Cr(VI)-reducing bacterium isolated from tannery activated sludge. Ecotoxicology and environmental safety 54 31629191
2001 CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation. Ophthalmic genetics 53 11559858
2015 A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 25878282
2013 CRB1: one gene, many phenotypes. Seminars in ophthalmology 49 24138049
2014 CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice. Human molecular genetics 46 24565864
2017 The CRB1 Complex: Following the Trail of Crumbs to a Feasible Gene Therapy Strategy. Frontiers in neuroscience 44 28424578
2024 CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut. Cell 42 38412859
2022 CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History. American journal of ophthalmology 41 36099972
2011 Homozygosity mapping identifies the Crumbs homologue 1 (Crb1) gene as responsible for a recessive syndrome of retinitis pigmentosa and nanophthalmos. American journal of medical genetics. Part A 40 21484995
2009 CRB1 gene mutations are associated with keratoconus in patients with leber congenital amaurosis. Investigative ophthalmology & visual science 40 19407021
2017 LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability. Retina (Philadelphia, Pa.) 38 27380427
2016 Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis. Investigative ophthalmology & visual science 37 27258436
2006 CRB1 heterozygotes with regional retinal dysfunction: implications for genetic testing of leber congenital amaurosis. Investigative ophthalmology & visual science 36 16936081
2019 Loss of CRB2 in Müller glial cells modifies a CRB1-associated retinitis pigmentosa phenotype into a Leber congenital amaurosis phenotype. Human molecular genetics 33 30239717
2023 AAV-mediated gene augmentation therapy of CRB1 patient-derived retinal organoids restores the histological and transcriptional retinal phenotype. Stem cell reports 31 37084726
2021 CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials. American journal of ophthalmology 31 34320374
2021 CRB1-associated retinal dystrophies in a Belgian cohort: genetic characteristics and long-term clinical follow-up. The British journal of ophthalmology 28 33579689
2013 Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1(rd8) background. Synapse (New York, N.Y.) 28 23592324
2013 Rd8 mutation in the Crb1 gene of CD11c-eYFP transgenic reporter mice results in abnormal numbers of CD11c-positive cells in the retina. Journal of neuropathology and experimental neurology 28 23860032
2020 Research Models and Gene Augmentation Therapy for CRB1 Retinal Dystrophies. Frontiers in neuroscience 26 32922261
2013 Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations. Investigative ophthalmology & visual science 26 23449718
2017 The correlation between CRB1 variants and the clinical severity of Brazilian patients with different inherited retinal dystrophy phenotypes. Scientific reports 25 28819299
2002 A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis. Ophthalmic genetics 24 12567265
2013 Childhood cone-rod dystrophy with macular cystic degeneration from recessive CRB1 mutation. Ophthalmic genetics 23 23767994
2021 Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies. Acta ophthalmologica 22 33528094
2021 Multimodal Retinal Imaging and Microperimetry Reveal a Novel Phenotype and Potential Trial End Points in CRB1-Associated Retinopathies. Translational vision science & technology 21 34003923
2020 AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model. Molecular therapy. Methods & clinical development 21 33575434
2016 Phenotypic features of CRB1-associated early-onset severe retinal dystrophy and the different molecular approaches to identifying the disease-causing variants. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 21 27113771
2016 Systemic inflammatory immune signatures in a patient with CRB1 linked retinal dystrophy. Expert review of clinical immunology 21 27690673
2006 A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis. Ophthalmic genetics 21 16543197
2008 Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both Stargardt disease and autosomal recessive retinitis pigmentosa. Molecular vision 20 18334942
2021 CRB1-Related Retinal Dystrophies in a Cohort of 50 Patients: A Reappraisal in the Light of Specific Müller Cell and Photoreceptor CRB1 Isoforms. International journal of molecular sciences 19 34884448
1999 Integrated genetic and physical map of the 1q31-->q32.1 region, encompassing the RP12 locus, the F13B and HF1 genes, and the EEF1AL11 and RPL30 pseudogenes. Cytogenetics and cell genetics 19 10343093
2019 Chromatic Full-Field Stimulus Threshold and Pupillography as Functional Markers for Late-Stage, Early-Onset Retinitis Pigmentosa Caused by CRB1 Mutations. Translational vision science & technology 18 31879567
2016 Coat's like vasculopathy in leber congenital amaurosis secondary to homozygous mutations in CRB1: a case report and discussion of the management options. BMC research notes 18 26872607
2015 Retinal Dystrophy with Intraretinal Cystoid Spaces Associated with Mutations in the Crumbs Homologue (CRB1) Gene. Ophthalmic genetics 18 24512366
2009 Case report: autofluorescence imaging and phenotypic variance in a sibling pair with early-onset retinal dystrophy due to defective CRB1 function. Current eye research 18 19401883
2004 The expanding roles of ABCA4 and CRB1 in inherited blindness. Novartis Foundation symposium 17 14750597
1991 DNA sequence of the ribosomal protein genes rp12 and rps19 from a plant-pathogenic mycoplasma-like organism. FEMS microbiology letters 17 1769558
2014 Novel mutations of CRB1 in Chinese families presenting with retinal dystrophies. Molecular vision 16 24715753
2013 Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family. European journal of human genetics : EJHG 16 23443024
2014 Detection of CRB1 mutations in families with retinal dystrophy through phenotype-oriented mutational screening. International journal of molecular medicine 15 24535598
2020 Characterization of CRB1 splicing in retinal organoids derived from a patient with adult-onset rod-cone dystrophy caused by the c.1892A>G and c.2548G>A variants. Molecular genetics & genomic medicine 14 32931148
2018 AAV Gene Augmentation Therapy for CRB1-Associated Retinitis Pigmentosa. Methods in molecular biology (Clifton, N.J.) 14 29188511
2004 Expression of a novel secretory form (Crb1s) of mouse Crumbs homologue Crb1 in skin development. Biochemical and biophysical research communications 13 14684155
1996 Fine mapping of the autosomal recessive retinitis pigmentosa locus (RP12) on chromosome 1q; exclusion of the phosducin gene (PDC). Cytogenetics and cell genetics 13 8646891
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2020 Transcriptomics analysis of Ccl2/Cx3cr1/Crb1rd8 deficient mice provides new insights into the pathophysiology of progressive retinal degeneration. Experimental eye research 12 33373623
2015 Mthfr as a modifier of the retinal phenotype of Crb1(rd8/rd8) mice. Experimental eye research 12 26646559
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2019 Targeted deletion of Crb1/Crb2 in the optic vesicle models key features of leber congenital amaurosis 8. Developmental biology 11 31145883
2023 Characterization and AAV-mediated CRB gene augmentation in human-derived CRB1KO and CRB1KOCRB2+/- retinal organoids. Molecular therapy. Methods & clinical development 10 37886604
2021 Defining Phenotype, Tropism, and Retinal Gene Therapy Using Adeno-Associated Viral Vectors (AAVs) in New-Born Brown Norway Rats with a Spontaneous Mutation in Crb1. International journal of molecular sciences 10 33808129
2020 DIFFUSE RETINAL VASCULAR LEAKAGE AND CONE-ROD DYSTROPHY IN A FAMILY WITH THE HOMOZYGOUS MISSENSE C.1429G>A (P.GLY477ARG) MUTATION IN CRB1. Retinal cases & brief reports 10 29200130
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2008 Early noninvasive prenatal detection of a fetal CRB1 mutation causing Leber congenital amaurosis. Molecular vision 10 18682814
2019 The Enigma of CRB1 and CRB1 Retinopathies. Advances in experimental medicine and biology 9 31884620
2014 Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy. Documenta ophthalmologica. Advances in ophthalmology 9 25323024
2020 CRB1rd8 mutation influences the age-related macular degeneration phenotype of NRF2 knockout mice and favors choroidal neovascularization. Advances in medical sciences 8 31918066
2020 Zebrafish Crb1, Localizing Uniquely to the Cell Membranes around Cone Photoreceptor Axonemes, Alleviates Light Damage to Photoreceptors and Modulates Cones' Light Responsiveness. The Journal of neuroscience : the official journal of the Society for Neuroscience 8 32817065
2019 CRB1 Gene Mutation Causing Different Phenotypes of Leber Congenital Amaurosis in Siblings. Journal of ophthalmic & vision research 8 31875109
2018 Expression and localization of the polarity protein CRB2 in adult mouse brain: a comparison with the CRB1rd8 mutant mouse model. Scientific reports 8 30076417
2017 Homozygosity Mapping and Targeted Sanger Sequencing Identifies Three Novel CRB1 (Crumbs homologue 1) Mutations in Iranian Retinal Degeneration Families. Iranian biomedical journal 8 28460491
2015 The retinal phenotype of Grk1-/- is compromised by a Crb1 rd8 mutation. Molecular vision 8 26664249
2013 Report of a novel mutation in CRB1 in a Lebanese family presenting retinal dystrophy. Ophthalmic genetics 8 23362850
2007 Overexpression of human CRB1 or related isoforms, CRB2 and CRB3, does not regulate the human presenilin complex in culture cells. Biochemistry 8 17988153
2024 Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis. BMC ophthalmology 7 38622537
2023 Generation of CRB1 RP Patient-Derived iPSCs and a CRISPR/Cas9-Mediated Homology-Directed Repair Strategy for the CRB1 c.2480G>T Mutation. Advances in experimental medicine and biology 7 37440088
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2020 CRB1 related retinal degeneration with novel mutation. American journal of ophthalmology case reports 7 32322752