Affinage

CRB1

Protein crumbs homolog 1 · UniProt P82279

Length
1406 aa
Mass
154.2 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRB1 is a large transmembrane protein with an extracellular array of EGF-like and laminin A G-like domains and a conserved cytoplasmic tail that organizes an apical polarity scaffold in the vertebrate retina, where its loss causes autosomal recessive retinitis pigmentosa (RP12) and Leber congenital amaurosis (PMID:10508521, PMID:11734541, PMID:31145883). The cytoplasmic domain is functionally interchangeable with that of Drosophila Crumbs and nucleates an intracellular scaffold (PMID:11734541) that recruits the MAGUK proteins MPP5/PALS1 and MPP4, with PALS1 required for correct CRB1 localization to the subapical region above adherens junctions in Müller glia (PMID:15914641, PMID:16885194). CRB1 also forms homomeric complexes and heteromeric complexes with CRB2 through their extracellular domains, and the two proteins co-localize at the subapical region of both photoreceptors and Müller glia at the outer limiting membrane (PMID:24565864, PMID:38570189). Through this scaffold CRB1 maintains external/outer limiting membrane integrity, adherens junction stability between photoreceptors and Müller glia, and apical Müller glia features; its loss produces fragmented junctions, displaced photoreceptors, shortened inner/outer segments, and focal degeneration (PMID:12915475, PMID:17234588, PMID:17705196). In retinal progenitor cells CRB1 acts redundantly with CRB2 to restrain proliferation and govern lamination, dysregulating Notch1 and YAP/Hippo signaling target genes when both are lost, and CRB1 interacts with NOTCH1 extracellularly while supporting RAB11A+ vesicle recycling and early endosome maturation (PMID:24339791, PMID:31145883, PMID:37541258). Beyond the retina, CRB1 is enriched at apical junctional complexes of retinal pigment epithelium and colonic enterocytes, where it maintains both the outer blood-retinal barrier and the intestinal epithelial barrier such that its loss permits gut bacterial translocation to the retina and secondary retinal degeneration (PMID:38412859). CRB2 functions as a genetic modifier and a key determinant of disease severity, and isoform/cell-type distribution of CRB expression is critical, with Müller-cell-enriched CRB1 isoforms central to early-onset disease (PMID:24565864, PMID:30239717, PMID:34884448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 High

    Established the gene's identity and disease link: cloning revealed a Crumbs-homologous multidomain transmembrane protein whose mutations cause autosomal recessive retinitis pigmentosa, framing CRB1 as a retinal polarity/cell-interaction factor.

    Evidence Suppression subtractive hybridization cloning, domain analysis, and mutation analysis in RP patients

    PMID:10508521

    Open questions at the time
    • Domain-level mechanism inferred from Crumbs homology, not directly tested
    • No protein partners identified yet
    • Subcellular localization within retina not resolved
  2. 2001 High

    Tested whether the human cytoplasmic tail is functionally conserved: Drosophila rescue showed the human and fly cytoplasmic domains are interchangeable, establishing that CRB1 organizes a Crumbs-like intracellular scaffold.

    Evidence Alternative splice variant cloning with Drosophila rescue and overexpression assays

    PMID:11734541

    Open questions at the time
    • Mammalian scaffold partners not yet identified
    • Did not define the relevant retinal cell type
  3. 2002 High

    Defined the cellular function in photoreceptors: Crumbs loss-of-function showed a requirement for zonula adherens integrity and spectrin cytoskeleton stabilization at the apical stalk, with CRB1 localizing to the corresponding mammalian inner segment subdomain.

    Evidence Drosophila loss-of-function genetics with immunolocalization in fly and mammalian retina

    PMID:11850625

    Open questions at the time
    • Spectrin link demonstrated in fly, not in mammalian CRB1
    • Direct molecular partners not mapped
  4. 2003 High

    Confirmed the in vivo mammalian requirement: rd8 mice and patient OCT showed CRB1 is essential for external/outer limiting membrane and adherens junction integrity, with disorganized, thickened retina implicating a developmental lamination role.

    Evidence rd8 mouse model with immunohistochemistry and histopathology; high-resolution OCT in patients

    PMID:12700176 PMID:12915475

    Open questions at the time
    • Strong genetic-background dependence pointed to unidentified modifiers
    • Molecular cause of junction fragmentation not resolved
  5. 2006 High

    Mapped the scaffold and its assembly hierarchy: MPP4 was identified as a CRB1-complex member via MPP5/PALS1, and PALS1 was shown to be required for CRB1 (and CRB2/MUPP1/Veli3) localization to the subapical region in Müller glia.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, immuno-EM, and RNAi knockdown in Müller glia with CRB1 rescue

    PMID:15914641 PMID:16885194

    Open questions at the time
    • Stoichiometry and structure of the assembled complex unresolved
    • Whether the same hierarchy operates in photoreceptors not tested
  6. 2007 Medium

    Distinguished trafficking from adhesion defects: a C249W extracellular-domain knock-in trafficked normally to the subapical region, yet Crb1 loss caused photoreceptor displacement from loss of photoreceptor-Müller glia adhesion.

    Evidence Crb1C249W knock-in mouse with immunolocalization, ophthalmoscopy, and expression profiling; Crb1-/- Müller glia phenotyping

    PMID:17234588 PMID:17705196

    Open questions at the time
    • Pttg1 downregulation link mechanistically unexplained
    • How specific mutations cause disease despite normal trafficking unclear
  7. 2013 High

    Revealed redundancy and a signaling output: combined Crb1/Crb2 ablation in progenitors restrained proliferation, altered cell cycle, and dysregulated Notch1 and YAP/Hippo target genes, linking the CRB complex to proliferation control.

    Evidence Conditional single and double knockout mice with ERG, cell cycle, and pathway expression analysis (idx 9, 10)

    PMID:23001562 PMID:24339791

    Open questions at the time
    • Direct biochemical coupling of CRB1 to Notch/Hippo machinery not shown here
    • Whether proliferation effect is cell-autonomous unresolved
  8. 2019 High

    Defined CRB2 as a modifier and the developmental window of pathology: human/NHP localization plus conditional double knockouts showed CRB2 dosage and cell-type distribution dictate RP- versus LCA-like disease, with progenitor-stage loss producing the earliest, most severe defects.

    Evidence Human/NHP immuno-EM, conditional double knockouts with cell-type-specific and early (mRx-Cre) drivers, ERG and histology (idx 11, 13, 14, 15, 16)

    PMID:24565864 PMID:25701872 PMID:30239717 PMID:30956116 PMID:31145883

    Open questions at the time
    • Mechanism of CRB1/CRB2 dosage sensitivity not defined
    • Why CRB2 (not CRB1) gene therapy rescues remains mechanistically open
  9. 2024 High

    Established direct molecular interactions and a systemic disease axis: reciprocal co-IP showed CRB1 forms homo- and CRB1-CRB2 heteromers via extracellular domains, and CRB1 loss at colonic and RPE junctions allows gut bacterial translocation driving secondary retinal degeneration.

    Evidence Retina-specific and cell-based reciprocal co-IP with CRB3 negative control; rd8 mouse antibiotic depletion and colonic CRB1 restoration with barrier assays (idx 17, 18)

    PMID:38412859 PMID:38570189

    Open questions at the time
    • Mild interaction loss for many extracellular missense mutants leaves their pathogenic mechanism unexplained
    • How barrier breach and bacterial translocation integrate with the intrinsic polarity defect unresolved
  10. 2023 Medium

    Connected CRB1 to receptor trafficking: patient organoids showed CRB1-NOTCH1 extracellular interaction and a requirement for RAB11A+ vesicle recycling and early endosome maturation, with retromer and endolysosomal disruption upon CRB1 loss.

    Evidence CRB1 patient versus isogenic iPSC retinal organoids with proximity ligation assay and vesicle quantification

    PMID:37541258

    Open questions at the time
    • Single-lab organoid study without in vivo confirmation
    • Whether CRB1 directly drives recycling or acts indirectly via junction loss unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structural scaffold function, Notch/Hippo signaling, vesicle recycling, and the epithelial barrier roles are mechanistically unified into a single CRB1 activity remains unresolved.
  • No structure of an assembled CRB1 complex
  • Causal ordering of polarity loss, signaling dysregulation, and barrier breach undefined
  • Genotype-phenotype mechanism for individual extracellular missense mutants not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0031410 cytoplasmic vesicle 1
Partners
CRB2MPP4MPP5MUPP1NOTCH1VELI3
Complex memberships
CRB1-CRB2 heteromeric complexCRB1/PALS1(MPP5)/MPP4 scaffold

Evidence

Reading pass · 23 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, and mutations in CRB1 cause autosomal recessive retinitis pigmentosa (RP12). The protein is expressed specifically in the human retina and RPE, and its homology to Crumbs suggests a role in cell-cell interaction and maintenance of cell polarity in the retina. Suppression subtractive hybridization cloning, cDNA sequencing, chromosomal mapping, mutation analysis (homozygous AluY insertion and missense mutations in RP patients) Nature genetics High 10508521
2001 CRB1 contains a functionally conserved cytoplasmic domain (72% similar to Drosophila Crumbs cytoplasmic domain). An alternatively spliced variant encodes this cytoplasmic domain. Rescue and overexpression experiments in Drosophila demonstrated that the human and fly cytoplasmic domains are functionally interchangeable, suggesting CRB1 organizes an intracellular protein scaffold in the human retina analogous to the Crumbs scaffold in Drosophila epithelial cells. Alternative splice variant cloning, Drosophila rescue assays, Drosophila overexpression experiments Human molecular genetics High 11734541
2002 Drosophila Crumbs (ortholog of human CRB1) localizes to the stalk subdomain of photoreceptor apical plasma membrane and is required to maintain zonula adherens integrity during rhabdomere morphogenesis. Crumbs also stabilizes the membrane-associated spectrin cytoskeleton in the photoreceptor stalk, a function mechanistically distinct from its role in epithelial apical-basal polarity. CRB1 localizes to the inner segment subdomain of mammalian photoreceptors, the corresponding structure to the Drosophila stalk. Loss-of-function Drosophila genetics, immunolocalization in Drosophila and mammalian retina, zonula adherens integrity assays, spectrin cytoskeleton analysis Nature High 11850625
2003 CRB1 is essential for external limiting membrane (ELM) integrity in the mammalian retina. Loss of CRB1 (rd8 mouse model, single base deletion causing frameshift and premature stop truncating the transmembrane and cytoplasmic domains) results in discontinuous and fragmented adherens junction proteins at the ELM, shortened photoreceptor inner and outer segments detectable as early as 2 weeks after birth, and photoreceptor dysplasia. The phenotype strongly varies with genetic background, suggesting interactions with modifier genes. Mouse knockout (rd8 spontaneous mutation), immunohistochemistry for adherens junction proteins, histopathology, genetic background analysis Human molecular genetics High 12915475
2003 CRB1 mutations in humans result in a retina that is remarkably thick in cross-section and lacks distinct layering, resembling immature normal retina. This abnormal retinal architecture suggests that the CRB1 disease pathway disturbs normal human retinal organization by interrupting naturally occurring apoptosis, consistent with a developmental role in retinal lamination. In vivo high-resolution optical coherence tomography (OCT) in patients with CRB1 mutations Human molecular genetics Medium 12700176
2005 MPP4 (a MAGUK protein) is a novel member of the CRB1 protein scaffold. MPP4 exists in a complex with CRB1 through direct interaction with MPP5 (PALS1). 3D homology modeling supports a mechanism regulating homo- and heterodimer recruitment of MPP4 and MPP5 to the CRB1 complex. CRB1, MPP5, and MPP4 colocalize at the outer limiting membrane (OLM) in the retina. Yeast two-hybrid screening, GST pull-down, co-immunoprecipitation, immunohistochemistry, immuno-electron 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) above adherens junctions in polarized Müller glia cells. Immuno-electron microscopy showed strong CRB1 immunoreactivity at the SAR specifically in Müller glia cells. RNA interference-mediated knockdown of Pals1 in Müller glia cells caused loss of CRB1, CRB2, MUPP1, and Veli3 localization at the SAR. Immuno-electron microscopy, immunohistochemistry, RNAi knockdown in primary retinal cultures, primary retinal Crb1-/- cultures rescued with human CRB1 Human molecular genetics High 16885194
2007 The Crb1(C249W) missense mutation (in the extracellular sixth calcium-binding EGF domain) does not prevent trafficking of CRB1 to the subapical region adjacent to adherens junctions at the OLM, indicating correct protein trafficking for this extracellular domain mutation in RP12 patients. Loss of Crb1 results in displaced photoreceptors and focal degeneration due to loss of adhesion between photoreceptors and Müller glia. Crb1 mutant retinas show lower levels of Pttg1 transcripts, with Pttg1 expression further decreased by light exposure. Knock-in mouse model (Crb1C249W), immunohistochemistry for subapical region localization, scanning laser ophthalmoscopy, gene expression analyses (microarray, RT-PCR) The Journal of neuroscience Medium 17234588
2007 Loss of Crb1 in Müller glia cells results in an irregular number and size of their apical villi, and subsequent loss of retinal integrity leading to neovascularization where choroidal blood vessels protrude into the neural retina. CRB1 is a determinant of apical Müller glia cell features, specifically regulating the number and size of apical villi. Crb1-/- mouse analysis, histology and immunohistochemistry, aging and light-exposure studies, gene expression profiling Glia Medium 17705196
2012 Loss of CRB2 in retinal progenitor cells causes progressive disorganization mimicking human retinitis pigmentosa associated with CRB1 mutations. CRB2 conditional knockout retinas show abnormal lamination of immature rod photoreceptors, disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells, increased numbers of late-born progenitor cells, rod photoreceptors and Müller glia, and programmed cell death of rod photoreceptors. This establishes CRB2 as an essential component of the CRB complex for photoreceptor layer lamination and suppression of late-born retinal progenitor proliferation. Conditional knockout mice, confocal scanning laser ophthalmoscopy, spectral domain OCT, electroretinography, histological analysis, cell counting Human molecular genetics High 23001562
2013 Combined ablation of CRB1 and CRB2 in retinal progenitor cells restrains proliferation of retinal progenitor cells. Loss of both proteins results in altered cell cycle progression, increased mitotic cells, and increased numbers of late-born cell types (rod photoreceptors, bipolar and Müller glia cells). Loss of CRB1 and CRB2 dysregulates Notch1 and YAP/Hippo signaling pathway target genes and increases P120-catenin levels. Conditional double knockout mice, electroretinography, histological analysis, cell cycle distribution analysis, gene expression analysis for Notch1 and YAP/Hippo targets, immunohistochemistry PLoS genetics High 24339791
2014 In the human retina, CRB1 protein is expressed at the subapical region in both photoreceptors and Müller glia cells, whereas CRB2 is expressed only in Müller glia cells (contrasting with mice where distributions differ). Genetic ablation of one allele of Crb2 in Crb1 heterozygous mice induces mild retinal phenotype; in homozygous Crb1 knockout mice it leads to early and severe phenotype throughout the inferior retina. This establishes CRB2 as a genetic modifier of CRB1-related retinal dystrophy. Immunohistochemistry in human retina, conditional mouse genetics (double mutant analysis), funduscopy, histology Human molecular genetics High 24565864
2015 A new CRB1 rat mutation (insertion-deletion in Crb1) causes dislocalization of CRB1 protein from retinal Müller glia/photoreceptor junctions, leading to progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of Müller glial cells. Transcriptomic analysis of primary Müller glia cultures identified dysregulated pathways including TGF-β, MAPK cascade, growth factor signaling, G-protein signaling, actin cytoskeleton regulation, and cardiovascular signaling, linking Müller glia dysfunction to retinal telangiectasia. Characterization of spontaneous rat mutant, genetic analysis, immunohistochemistry, transcriptomic analysis of primary RMG cultures The Journal of neuroscience Medium 25878282
2015 Gene therapy targeting both Müller glia cells and photoreceptors with CRB2 (not CRB1) vectors ameliorated retinal function and structure in Crb1 mouse models. Targeting only a single cell type (Müller glia OR photoreceptors) with CRB2 was insufficient. Surprisingly, targeting cells with CRB1 vectors reduced retinal function, indicating that the level and distribution of CRB expression across cell types is critical for function. AAV gene delivery to Crb1 retinitis pigmentosa mouse models, electroretinography, optical coherence tomography, immunohistochemistry Human molecular genetics Medium 25701872
2019 Human CRB1 and CRB2 co-localize in developing human fetal retina and iPSC-derived retinal organoids; CRB2 protein expression precedes CRB1 during human retinal development. Both CRB1 and CRB2 are present in human photoreceptors and Müller glial cells. CRB1 patient iPSC retinal organoids recapitulate disruptions at the outer limiting membrane as found in Crb1 mutant mice. Human fetal retina immunohistochemistry, iPSC-derived retinal organoids, CRB1 patient iPSC organoids, protein co-localization Stem cell reports Medium 30956116
2019 Loss of CRB2 specifically in Müller glial cells, in the context of CRB1 knockout, converts a CRB1-associated retinitis pigmentosa-like phenotype into a Leber congenital amaurosis-like phenotype in mice. Non-human primate (NHP) CRB1 and CRB2 proteins both localize to the subapical region adjacent to adherens junctions at the outer limiting membrane in both Müller glia cells and photoreceptors. Conditional double knockout mice (Müller glia-specific), electroretinography, histology, immuno-electron microscopy in NHP retina Human molecular genetics High 30239717
2019 Combined ablation of Crb1 and Crb2 from the optic vesicle stage (using mRx-Cre) results in severe retinal defects including locally thickened retina, aberrant positioning of retinal cells, disrupted lamination, and severely attenuated electroretinogram at eye-opening. Retinal defects precede E12.5, indicating that LCA8 pathology arises from malfunction of retinal progenitor cells during early development rather than from defective photoreceptor-Müller glia interaction. Conditional double knockout mice using mRx-Cre driver, electroretinography, histology, developmental staging Developmental biology High 31145883
2024 Human canonical CRB1 interacts with CRB1 (homomerically) and CRB2 (heteromerically) through their extracellular domains, forming homo- and heteromeric complexes in the human retina. CRB1 does not interact with CRB3, which lacks an extracellular domain. CRB1 and CRB2 co-localize in human retina and iPSC-derived retinal organoids. Various CRB1 and CRB2 missense mutations in the extracellular domain showed no or only mild loss of CRB1-CRB2 interaction in vitro. Co-immunoprecipitation in retina-specific pull-downs, co-IP from transfected cells with various CRB mutants, immunohistochemistry/co-localization in human retina and iPSC organoids Life science alliance High 38570189
2024 Normal CRB1 expression is enriched at apical junctional complexes of retinal pigment epithelium and colonic enterocytes. The Rd8 mutation in Crb1 dampens CRB1 expression at both sites, impairing both the outer blood-retinal barrier and the colonic intestinal epithelial barrier. This leads to translocation of intestinal bacteria from the lower GI tract to the retina, causing secondary retinal degeneration. Depletion of bacteria systemically or reintroduction of normal Crb1 expression colonically rescued retinal degeneration without reversing the retinal barrier breach. Immunohistochemistry for CRB1 localization, bacterial detection in retinal lesions, antibiotic treatment in Rd8 mice, colonic CRB1 gene restoration, outer blood-retinal barrier assessment Cell High 38412859
2023 CRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids. CRB1 patient organoids show decreased CRB1 and NOTCH1 expression at the outer limiting membrane. Proximity ligation assays demonstrate that human CRB1 and NOTCH1 can interact via their extracellular domains. CRB1 patient organoids exhibit increased WDFY1+ vesicles, fewer RAB11A+ recycling endosomes, decreased VPS35 retromer complex components, and more degradative endolysosomal compartments, indicating impaired early endosome maturation and receptor recycling. CRB1 patient iPSC-derived retinal organoids, proximity ligation assay, immunohistochemistry, vesicle quantification, comparison with isogenic gene-corrected controls Stem cell reports Medium 37541258
2004 A novel secretory isoform of mouse Crb1 (Crb1s) was identified, arising from retention of the 3' end of exon 6, encoding a short secretory protein lacking transmembrane and cytoplasmic domains. Crb1s is expressed in various tissues (skin, lung, kidney) in contrast to canonical Crb1 (brain and eye only). In cultured keratinocytes, Crb1s is secreted as an ~80 kDa processed form. After Ca2+-induced differentiation, Crb1s becomes associated with focal adhesions and cell-cell contacts. cDNA cloning, Northern blot, Western blot, cell culture secretion assays, immunolocalization in keratinocytes Biochemical and biophysical research communications Medium 14684155
2007 Overexpression of human CRB1 (or CRB2 or CRB3) in mammalian culture cells does not interact with presenilin complex components (NCT, Aph1, Pen2) and does not affect levels of presenilin complex components, NCT maturation, PS endoproteolysis, or Aβ, AICD, or NICD production. This is a negative finding: human CRB1 does not regulate the presenilin/gamma-secretase complex in cultured mammalian cells. Co-immunoprecipitation, Western blot for presenilin complex components, Aβ/AICD/NICD production assays in overexpression cell systems Biochemistry Medium 17988153
2021 CRB1 isoforms differ in their cell-type localization: a canonical long isoform A (12 exons) is localized in Müller cells while a short isoform B (7 exons) is predominant in photoreceptors. Clinical re-analysis of 50 patients indicates that severe Müller cell impairment is consistently associated with early-onset retinal dystrophy, with variants specifically affecting exon 12 (Müller-cell isoform A) causing severe disease even when isoform B remains wild-type. Isoform characterization (RT-PCR, sequencing), patient cohort genotype-phenotype re-analysis with isoform-specific variant assessment, immunohistochemistry International journal of molecular sciences Medium 34884448

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 600 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 323 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 286 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 167 22065545
2004 CRB1 mutation spectrum in inherited retinal dystrophies. Human mutation 156 15459956
2002 Isolation of Crb1, a mouse homologue of Drosophila crumbs, and analysis of its expression pattern in eye and brain. Mechanisms of development 100 11744384
2010 Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1. The British journal of ophthalmology 99 20956273
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 88 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 80 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 78 16272259
2012 Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to mutations in the CRB1 gene. Human molecular genetics 73 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 71 17234588
2015 Gene therapy into photoreceptors and Müller glial cells restores retinal structure and function in CRB1 retinitis pigmentosa mouse models. Human molecular genetics 70 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 56 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 50 24138049
2024 CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut. Cell 48 38412859
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 45 28424578
2022 CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History. American journal of ophthalmology 43 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 41 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
2023 AAV-mediated gene augmentation therapy of CRB1 patient-derived retinal organoids restores the histological and transcriptional retinal phenotype. Stem cell reports 35 37084726
2021 CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials. American journal of ophthalmology 34 34320374
2019 Loss of CRB2 in Müller glial cells modifies a CRB1-associated retinitis pigmentosa phenotype into a Leber congenital amaurosis phenotype. Human molecular genetics 34 30239717
2021 CRB1-associated retinal dystrophies in a Belgian cohort: genetic characteristics and long-term clinical follow-up. The British journal of ophthalmology 29 33579689
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 29 23860032
2020 Research Models and Gene Augmentation Therapy for CRB1 Retinal Dystrophies. Frontiers in neuroscience 28 32922261
2013 Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1(rd8) background. Synapse (New York, N.Y.) 28 23592324
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 27 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
2006 A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis. Ophthalmic genetics 23 16543197
2021 Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies. Acta ophthalmologica 22 33528094
2020 AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model. Molecular therapy. Methods & clinical development 22 33575434
2016 Systemic inflammatory immune signatures in a patient with CRB1 linked retinal dystrophy. Expert review of clinical immunology 22 27690673
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
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
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 20 34884448
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
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
2023 Clinical and Therapeutic Evaluation of the Ten Most Prevalent CRB1 Mutations. Biomedicines 13 36830922
2023 Foveal Hypoplasia in CRB1-Related Retinopathies. International journal of molecular sciences 13 37762234
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
2023 CRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids. Stem cell reports 12 37541258
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
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
2019 Cytoglobin deficiency potentiates Crb1-mediated retinal degeneration in rd8 mice. Developmental biology 10 31634437
2019 Microglial Cell Dysfunction in CRB1-Associated Retinopathies. Advances in experimental medicine and biology 10 31884605
2018 Expression and localization of the polarity protein CRB2 in adult mouse brain: a comparison with the CRB1rd8 mutant mouse model. Scientific reports 10 30076417
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
2024 Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina. Life science alliance 8 38570189
2024 Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis. BMC ophthalmology 8 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 8 37440088
2022 CRB1-associated retinal dystrophy presenting as self-resolving opsoclonus and posterior uveitis. American journal of ophthalmology case reports 8 35243176
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
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

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