Affinage

PDE6B

Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta · UniProt P35913

Length
854 aa
Mass
98.3 kDa
Annotated
2026-04-29
100 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDE6B encodes the beta catalytic subunit of rod photoreceptor cGMP phosphodiesterase 6 (PDE6), which hydrolyzes cGMP as the effector step in the visual phototransduction cascade. PDE6B and PDE6A catalytic subunits are enzymatically equivalent in cGMP hydrolysis kinetics (Km ~20–23 µM) and sensitivity to inhibitory PDE6γ subunits, though the native rod PDE6 heterodimer requires higher transducin-α concentrations for activation than homodimeric chimeras (PMID:20940301). The H258N mutation impairs PDE6γ-mediated inhibition, causing constitutive cGMP hydrolytic hyperactivity and congenital stationary night blindness, while loss-of-function mutations cause photoreceptor degeneration through cGMP accumulation, calcium overload, CaMKII-driven phosducin hyperphosphorylation, calpain activation, and mitochondrial stress (PMID:17044014, PMID:16253986, PMID:16405498, PMID:35075486). Loss-of-function mutations in PDE6B cause autosomal recessive retinitis pigmentosa in humans and progressive retinal atrophy in dogs, with phenotypic severity correlating with allele severity (PMID:8595886, PMID:16123450, PMID:11124530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1995 High

    Establishing PDE6B as a disease gene: identification of compound heterozygous PDE6B mutations in patients with autosomal recessive retinitis pigmentosa demonstrated that loss of the rod PDE6 beta subunit causes human retinal degeneration.

    Evidence Haplotype analysis, DGGE/SSCP, and sequencing of all 22 PDE6B exons in affected families

    PMID:8595886

    Open questions at the time
    • Functional impact of individual mutations not biochemically characterized
    • Genotype-phenotype severity relationship not yet established
  2. 2000 Medium

    Cross-species validation: an 8-bp insertion in PDE6B exon 21 cosegregating with generalized progressive retinal atrophy in Sloughi dogs confirmed PDE6B as a conserved cause of photoreceptor degeneration across species.

    Evidence Cosegregation analysis of PDE6B mutation in canine pedigree

    PMID:11124530

    Open questions at the time
    • Biochemical consequence of the canine insertion not characterized
    • Retinal cell-type specificity of degeneration not examined
  3. 2005 High

    An allelic series and downstream death pathways were defined: ENU-generated Pde6b alleles showed that null mutations cause rapid degeneration while hypomorphic alleles cause slower progression, and rd1 retinas revealed that calcium overload from absent cGMP hydrolysis drives CaMKII overactivation (constitutive phosducin hyperphosphorylation) and calpain activation as mediators of photoreceptor death.

    Evidence ENU mutagenesis with phenotypic grading; 2D-gel proteomics, phosphorylation assays, and enzymatic calpain activity assays in rd1 vs wild-type retina

    PMID:16123450 PMID:16253986 PMID:16405498

    Open questions at the time
    • Whether CaMKII or calpain activation is sufficient or necessary for cell death not tested by genetic epistasis
    • Relative contribution of each death pathway to overall degeneration unclear
  4. 2007 High

    A gain-of-function mechanism was resolved: the H258N missense mutation impairs PDE6γ-mediated inhibition of PDE6β, causing ~3-fold elevated basal cGMP hydrolysis in dark-adapted retina and congenital stationary night blindness, while still rescuing photoreceptor survival in rd1 mice.

    Evidence Transgenic mouse expression of H258N PDE6B with retinal cGMP-PDE activity assay, ERG, and histological rescue of rd1

    PMID:17044014

    Open questions at the time
    • Structural basis of impaired PDE6γ interaction not resolved
    • Whether H258N alters transducin-mediated activation not tested
  5. 2010 High

    Catalytic equivalence of PDE6A and PDE6B was established: chimeric homodimeric enzymes showed indistinguishable kcat, Km, and PDE6γ sensitivity, but the native heterodimer required higher transducin-α for activation, indicating heterodimer-specific regulatory properties.

    Evidence Chimeric PDE6C-A and PDE6C-B homodimers expressed in transgenic Xenopus with in vitro kinetic and inhibition assays

    PMID:20940301

    Open questions at the time
    • Structural basis for heterodimer-specific transducin sensitivity unknown
    • Role of GAF domains in subunit-specific regulation not addressed
  6. 2015 High

    Gene replacement therapy restored PDE6B-dependent photoreceptor function: AAV-delivered PDE6B rescued the ERG a-wave in rd1 mice, but full circuit restoration required correction of a confounding Gpr179 mutation, demonstrating durable (13-month) functional rescue.

    Evidence AAV-mediated gene delivery with ERG recording, genetic backcross to remove Gpr179 mutation

    PMID:25613321

    Open questions at the time
    • Long-term safety and photoreceptor survival beyond 13 months not reported
    • Whether gene replacement reverses ongoing degeneration (as opposed to preventing it) not tested
  7. 2022 Medium

    Mitochondrial stress was identified as an early driver of PDE6B-deficient photoreceptor death: multiomics profiling of rd1 retina revealed early calcium-driven mitochondrial overactivation with partial bypass of complex I electron transfer, preceding the onset of cell death.

    Evidence Temporal transcriptomics, quantitative proteomics, ex vivo oxygen consumption, and TEM in neonatal rd1 retina

    PMID:35075486

    Open questions at the time
    • Whether mitochondrial stress is causative or correlative not established by intervention
    • Relationship between mitochondrial dysfunction and calpain/CaMKII pathways not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for heterodimer-specific transducin regulation, the relative causal contributions of calpain, CaMKII, and mitochondrial pathways to photoreceptor death, and whether therapeutic intervention targeting these downstream pathways can synergize with gene replacement remain unresolved.
  • No high-resolution structure of the PDE6αβ heterodimer with transducin
  • No genetic epistasis experiments separating calpain, CaMKII, and mitochondrial death pathways
  • No combinatorial gene replacement + neuroprotection trials reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2
Pathway
R-HSA-9709957 Sensory Perception 5 R-HSA-162582 Signal Transduction 3
Partners
PDE6APDE6G
Complex memberships
Rod PDE6 (PDE6αβγγ)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The unique N-terminal 25-amino acid domain of PDE4A splice variant RD1 (RNPDE4A1A) is required for plasma membrane association; deletion of this domain (Met26-RD1) causes exclusive cytosolic localization. Membrane-associated RD1 exhibits enhanced thermostability (t0.5 ~11 min vs ~3 min for cytosolic form), which is lost upon detergent solubilization. The N-terminal domain does not alter substrate specificity, Km for cAMP (~4 µM), or sensitivity to rolipram inhibition (Ki ~0.5 µM). Truncation mutagenesis, subcellular fractionation, Triton X-114 phase separation, thermal inactivation assays in transfected COS cells The Biochemical journal High 7686364
1995 Native RD1 (RNPDE4A1A) is expressed in cerebellum as an ~73 kDa integral membrane protein predominantly (~93%) associated with the plasma membrane, co-localizing with the plasma membrane marker 5'-nucleotidase in synaptosomes enriched in post-synaptic densities. The enzyme is cAMP-specific (Km ~2.3 µM), rolipram-sensitive (Ki ~0.7 µM), Ca2+/calmodulin-insensitive, and is not anchored by N-terminal acylation. Deletion of the 25-residue N-terminal domain caused ~2-fold increase in Vmax and exclusive cytosolic redistribution. Subcellular fractionation, immunoprecipitation of PDE activity, laser scanning confocal and digital deconvolution immunofluorescence, sucrose density gradient fractionation, [3H]palmitate labeling, hydroxylamine treatment, truncation mutagenesis in transfected COS cells The Biochemical journal High 7702577
1995 The unique N-terminal 25-residue splice region of RD1 (RNPDE4A1) is sufficient to confer membrane association upon the soluble cytosolic protein chloramphenicol acetyltransferase (CAT) when fused as a chimera, directing the chimera to the plasma membrane fraction in COS-7 cells. Residues 1–25 are sufficient; residues 26–100 are not. Chimeric construct expression in COS-7 cells, subcellular fractionation, detergent solubilization The Biochemical journal High 7772057
1996 The membrane-targeting domain of RD1 (RNPDE4A1) N-terminal splice region consists of two helical sub-regions: an N-terminal amphipathic alpha-helix and a compact hydrophobic tryptophan-rich domain (residues 14–20). NMR structure shows the tryptophan-rich domain forms a hydrophobic cluster (Pro14, Trp15, Leu16, Trp19, Trp20). Deletion of this tryptophan-rich domain abolishes membrane association, while replacement with seven alanines also abolishes it, indicating membrane association depends on specific hydrophobic interactions rather than bulk hydrophobicity. 1H NMR structure determination of synthetic 25-residue peptide; deletion/substitution chimeric constructs with CAT in in vitro membrane binding assay The Journal of biological chemistry High 8663181
1997 In stably transfected human follicular thyroid carcinoma cells (FTC133A, FTC236A), RD1 (RNPDE4A1A) activity is exclusively membrane-associated and immunoreactive RD1 localizes to a discrete perinuclear region co-localizing with the Golgi apparatus marker. Treatment with monensin or brefeldin A redistributes both Golgi markers and RD1 similarly, indicating Golgi targeting in these cell lines. Stable transfection, subcellular fractionation, laser scanning confocal immunofluorescence, Golgi-disrupting agents (monensin, brefeldin A) The Biochemical journal Medium 9003417
1995 Mutations in the PDE6B gene (encoding the beta subunit of rod cGMP phosphodiesterase) cause autosomal recessive retinitis pigmentosa in humans. Two compound heterozygous probands were identified: one with Gly576Asp and His620 1-bp deletion mutations, and another with a Lys706X null mutation and an AG-to-AT splice acceptor site mutation in intron 2. Haplotype analysis, DGGE, SSCP electrophoresis, DNA sequencing of all 22 PDE6B exons Genomics High 8595886
2010 PDE6A and PDE6B catalytic subunits of rod PDE6 are enzymatically equivalent: chimeric homodimeric enzymes containing the PDE6A or PDE6B catalytic domain (expressed as EGFP-PDE6C-A and EGFP-PDE6C-B in transgenic Xenopus) showed similar cGMP hydrolysis kinetics (Km 20–23 µM, kcat 4200–5100 s⁻¹), comparable inhibition by both cone and rod Pγ subunits, and full activation by both cone and rod transducin-α. Both PDE6C-A and PDE6C-B were targeted to rod outer segments and concentrated at disc rims. However, rod PDE6 heterodimer requires higher concentrations of transducin-α for half-maximal activation than the homodimeric chimeras. Chimeric enzyme expression in transgenic Xenopus laevis, selective immunoprecipitation, in vitro cGMP hydrolysis assays, inhibition kinetics The Journal of biological chemistry High 20940301
2007 The H258N mutation in PDE6B (associated with congenital stationary night blindness) causes an approximately 3-fold increase in the rate of retinal cGMP hydrolysis in dark-adapted transgenic mice (319.2 vs 130.1 nmol·min⁻¹·nmol⁻¹ rhodopsin), consistent with impaired inhibition of PDE6β activity by the regulatory PDE6γ subunit. The H258N transgene rescued photoreceptor degeneration in rd1 (Pde6b^rd1) mice. Transgenic mouse generation, cGMP-PDE6 activity assay in retinal extracts, electroretinography, histology Human mutation High 17044014
2005 Point mutations in Pde6b (three premature stop codons, two missense mutations, two splice mutations) generated by ENU mutagenesis cause retinal degeneration with severity correlated to the nature of the mutation: null alleles (stop codons and one splice mutation) cause rapid degeneration indistinguishable from rd1, while hypomorphic alleles (missense and the other splice mutation) show slower progression, demonstrating genotype-phenotype correlation for PDE6B. ENU mutagenesis, conformation-sensitive capillary electrophoresis, DNA sequencing, visual acuity testing, fundus examination, retinal histology Investigative ophthalmology & visual science High 16123450
2005 In rd1 (Pde6b mutant) retina, phosducin is constitutively hyperphosphorylated regardless of light status (unlike wild-type where phosphorylation is dark-dependent), coinciding with constitutive activation of Ca2+/calmodulin-activated protein kinase II (CaMKII) in rod outer segments. Increased rod calcium (due to absent cGMP hydrolysis) drives CaMKII overactivation, which phosphorylates phosducin as a substrate, representing an early pathogenic step. 2D gel electrophoresis proteomics, mass spectrometry identification, immunoblotting, phosphorylation assays, light/dark adaptation experiments in rd1 vs wild-type retina Molecular & cellular proteomics Medium 16253986
2006 Calpain activity is substantially increased in rd1 photoreceptors, peaking at postnatal day 13 coincident with peak photoreceptor cell death. Calpastatin (endogenous calpain inhibitor) and CREB-1 expression are reduced. Calpain-specific inhibitors decrease calpain activity in situ, implicating calpain activation as a mediator of rd1 photoreceptor death downstream of elevated calcium caused by the PDE6B mutation. Microarray, immunofluorescence, immunoblotting, enzymatic in situ calpain activity assay, pharmacological inhibition in rd1 retinal explants Journal of neurochemistry Medium 16405498
2000 An 8-bp insertion after codon 816 in exon 21 of the PDE6B gene cosegregates with generalized progressive retinal atrophy (gPRA) in Sloughi dogs, establishing PDE6B as the causative gene in this canine model. In 11 other dog breeds, PDE6B mutations did not segregate with gPRA, excluding it as the causative gene in those breeds. Genomic library isolation, SSCP analysis, mutation identification, cosegregation analysis in pedigree Cytogenetics and cell genetics Medium 11124530
2022 In rd1 (Pde6b^rd1/rd1) mouse neonatal photoreceptors, transcriptome profiling revealed early downregulation of anabolic and energy metabolism genes, and quantitative proteomics showed early changes in calcium signaling and oxidative phosphorylation with specific partial bypass of complex I electron transfer, preceding the onset of cell death. Ex vivo oxygen consumption assays and TEM confirmed progressive mitochondrial overactivation and structural abnormalities in rd1 rods, implicating aberrant calcium signaling as an initiator of mitochondrial stress as an early driver of PDE6B-deficiency-induced photoreceptor death. Temporal transcriptomics, quantitative proteomics, ex vivo oxygen consumption assay, transmission electron microscopy, metabolomics in rd1 retina Human molecular genetics Medium 35075486
2013 A three-base deletion in exon 21 of PDE6B causes an early-onset retinal degeneration (crd1) in American Staffordshire terriers, with structural photoreceptor abnormalities (abnormal rod and cone inner/outer segments) as early as 11 weeks, providing a large animal model of PDE6B-associated disease. Genome-wide association study, candidate gene sequencing, retinal morphology by light microscopy Investigative ophthalmology & visual science Medium 24045995
2015 Gene supplementation of rd1 mice (Pde6b mutant) with AAV-delivered PDE6B restores the photoreceptor-mediated a-wave of the ERG but fails to restore the bipolar cell-mediated b-wave unless a confounding Gpr179 mutation is also corrected. Backcrossing rd1 mice to remove the Gpr179 mutation followed by AAV-Pde6b gene replacement successfully restores both photoreceptor and bipolar cell function for up to 13 months. AAV-mediated gene delivery, ERG recording, genetic backcross, Gpr179 mutation identification by sequencing Nature communications High 25613321

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Molecular microbiology 568 12410828
2002 Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation. The Journal of infectious diseases 461 12508154
2004 A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. Molecular microbiology 328 15341647
2000 Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. The Journal of infectious diseases 290 11133379
2017 Microglia Polarization with M1/M2 Phenotype Changes in rd1 Mouse Model of Retinal Degeneration. Frontiers in neuroanatomy 195 28928639
2000 Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides. Infection and immunity 161 10816479
2005 A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Molecular microbiology 152 16135231
2017 iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice. Stem cell reports 142 28076757
2012 Long-term characterization of retinal degeneration in rd1 and rd10 mice using spectral domain optical coherence tomography. Investigative ophthalmology & visual science 120 22562504
2011 Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection. Proceedings of the National Academy of Sciences of the United States of America 120 21427227
2006 Calpain is activated in degenerating photoreceptors in the rd1 mouse. Journal of neurochemistry 113 16405498
1993 Engineered deletion of the unique N-terminal domain of the cyclic AMP-specific phosphodiesterase RD1 prevents plasma membrane association and the attainment of enhanced thermostability without altering its sensitivity to inhibition by rolipram. The Biochemical journal 113 7686364
2010 Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse. Cell death & disease 110 21364632
2001 A simple polymerase chain reaction assay for genotyping the retinal degeneration mutation (Pdeb(rd1)) in FVB/N-derived transgenic mice. Laboratory animals 106 11315164
1995 Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. Genomics 106 8595886
2004 The RD1 virulence locus of Mycobacterium tuberculosis regulates DNA transfer in Mycobacterium smegmatis. Proceedings of the National Academy of Sciences of the United States of America 103 15314236
2003 PPE protein (Rv3873) from DNA segment RD1 of Mycobacterium tuberculosis: strong recognition of both specific T-cell epitopes and epitopes conserved within the PPE family. Infection and immunity 94 14573626
2003 The RD1 proteins of Mycobacterium tuberculosis: expression in Mycobacterium smegmatis and biochemical characterization. Microbes and infection 93 14554249
1995 Identification and characterization of the type-IVA cyclic AMP-specific phosphodiesterase RD1 as a membrane-bound protein expressed in cerebellum. The Biochemical journal 85 7702577
2004 Cell envelope protein PPE68 contributes to Mycobacterium tuberculosis RD1 immunogenicity independently of a 10-kilodalton culture filtrate protein and ESAT-6. Infection and immunity 81 15039340
2015 Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179. Nature communications 79 25613321
2006 Accuracy of an immune diagnostic assay based on RD1 selected epitopes for active tuberculosis in a clinical setting: a pilot study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 78 16700703
2006 CNTF+BDNF treatment and neuroprotective pathways in the rd1 mouse retina. Brain research 77 17156753
2005 Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina. Molecular vision 74 16163266
2005 Genotype-phenotype correlation of mouse pde6b mutations. Investigative ophthalmology & visual science 72 16123450
2004 Genomic interrogation of the dassie bacillus reveals it as a unique RD1 mutant within the Mycobacterium tuberculosis complex. Journal of bacteriology 71 14679230
2014 Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina. Journal of neurophysiology 70 25008417
2011 IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy. BMC infectious diseases 70 21595874
2008 Role of M. tuberculosis RD-1 region encoded secretory proteins in protective response and virulence. Tuberculosis (Edinburgh, Scotland) 68 18640874
2009 Behavioral validation of the Ts65Dn mouse model for Down syndrome of a genetic background free of the retinal degeneration mutation Pde6b(rd1). Behavioural brain research 67 19720087
2007 Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse. Investigative ophthalmology & visual science 67 17962473
2004 Evaluation of T-cell responses to novel RD1- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection. Infection and immunity 66 15102765
2011 Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease among RD1-responders. PloS one 65 21479248
2017 Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina. Gene therapy 60 28872643
2013 Review: the history and role of naturally occurring mouse models with Pde6b mutations. Molecular vision 59 24367157
2007 Response to region of difference 1 (RD1) epitopes in human immunodeficiency virus (HIV)-infected individuals enrolled with suspected active tuberculosis: a pilot study. Clinical and experimental immunology 59 17680823
2001 Immunological characterization of antigens encoded by the RD1 region of the Mycobacterium tuberculosis genome. Scandinavian journal of immunology 59 11696195
2001 Calcium channel blocker D-cis-diltiazem does not slow retinal degeneration in the PDE6B mutant rcd1 canine model of retinitis pigmentosa. Molecular vision 58 11239245
1995 Chimeric constructs show that the unique N-terminal domain of the cyclic AMP phosphodiesterase RD1 (RNPDE4A1A; rPDE-IVA1) can confer membrane association upon the normally cytosolic protein chloramphenicol acetyltransferase. The Biochemical journal 57 7772057
2007 Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to Mycobacterium tuberculosis: a pilot study. Respiratory research 56 17257436
2006 Electrical stimulation in normal and retinal degeneration (rd1) isolated mouse retina. Vision research 55 16723150
2005 Intravitreous injection of PLGA microspheres encapsulating GDNF promotes the survival of photoreceptors in the rd1/rd1 mouse. Molecular vision 55 16319820
2015 Protective Effects of Human iPS-Derived Retinal Pigmented Epithelial Cells in Comparison with Human Mesenchymal Stromal Cells and Human Neural Stem Cells on the Degenerating Retina in rd1 mice. Stem cells (Dayton, Ohio) 54 25728228
2000 Generalized progressive retinal atrophy of Sloughi dogs is due to an 8-bp insertion in exon 21 of the PDE6B gene. Cytogenetics and cell genetics 54 11124530
2014 Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration. PloS one 53 24489706
2005 Differential modification of phosducin protein in degenerating rd1 retina is associated with constitutively active Ca2+/calmodulin kinase II in rod outer segments. Molecular & cellular proteomics : MCP 52 16253986
2008 Efficient testing of large pools of Mycobacterium tuberculosis RD1 peptides and identification of major antigens and immunodominant peptides recognized by human Th1 cells. Clinical and vaccine immunology : CVI 50 18400977
2007 Cellular responses to photoreceptor death in the rd1 mouse model of retinal degeneration. Investigative ophthalmology & visual science 50 17251487
2002 Immunogenicity of Mycobacterium tuberculosis RD1 region gene products in infected cattle. Clinical and experimental immunology 49 12296851
2016 Carnosic acid slows photoreceptor degeneration in the Pde6b(rd10) mouse model of retinitis pigmentosa. Scientific reports 48 26961159
2011 Spontaneous Oscillatory Rhythm in Retinal Activities of Two Retinal Degeneration (rd1 and rd10) Mice. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 47 22359480
2008 Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family. European journal of human genetics : EJHG 47 18854872
2015 Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice. Frontiers in cellular neuroscience 46 26379501
1999 Identification of a novel protein antigen encoded by a Mycobacterium tuberculosis-specific RD1 region gene. Scandinavian journal of immunology 46 10320645
1996 Determination of the structure of the N-terminal splice region of the cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and identification of the membrane association domain using chimeric constructs. The Journal of biological chemistry 46 8663181
2010 Rod phosphodiesterase-6 PDE6A and PDE6B subunits are enzymatically equivalent. The Journal of biological chemistry 43 20940301
2016 Neural stem cells transplanted to the subretinal space of rd1 mice delay retinal degeneration by suppressing microglia activation. Cytotherapy 42 27067610
2018 DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice. Cell death & disease 40 29472543
2010 Do calcium channel blockers rescue dying photoreceptors in the Pde6b ( rd1 ) mouse? Advances in experimental medicine and biology 40 20238051
2019 Rescue of Retinal Degeneration in rd1 Mice by Intravitreally Injected Metformin. Frontiers in molecular neuroscience 39 31080404
2013 IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Investigative ophthalmology & visual science 39 24045995
2006 FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant, a sighted variant of the FVB/N mouse strain suitable for behavioral analysis. Genes, brain, and behavior 39 17083330
2007 Transgenic mice carrying the H258N mutation in the gene encoding the beta-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness. Human mutation 38 17044014
2022 Multiomics analyses reveal early metabolic imbalance and mitochondrial stress in neonatal photoreceptors leading to cell death in Pde6brd1/rd1 mouse model of retinal degeneration. Human molecular genetics 37 35075486
2008 Response to M. tuberculosis selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis: a pilot study. BMC infectious diseases 37 18226199
2013 PdeB, a cyclic Di-GMP-specific phosphodiesterase that regulates Shewanella oneidensis MR-1 motility and biofilm formation. Journal of bacteriology 36 23794617
2012 Functional integrity and modification of retinal dopaminergic neurons in the rd1 mutant mouse: roles of melanopsin and GABA. Journal of neurophysiology 32 23255724
2009 Utility of a combination of RD1 and RD2 antigens as a diagnostic marker for tuberculosis. Diagnostic microbiology and infectious disease 31 19833469
2005 Does GDNF exert its neuroprotective effects on photoreceptors in the rd1 retina through the glial glutamate transporter GLAST? Molecular vision 30 16163265
2021 Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats. Experimental & molecular medicine 29 33828232
2005 Effects of the rd1 mutation and host strain on hippocampal learning in mice. Behavior genetics 28 16184487
1997 Intracellular localization of the PDE4A cAMP-specific phosphodiesterase splice variant RD1 (RNPDE4A1A) in stably transfected human thyroid carcinoma FTC cell lines. The Biochemical journal 28 9003417
2007 Single-stranded oligonucleotide-mediated in vivo gene repair in the rd1 retina. Molecular vision 27 17563719
2005 Differential Akt activation in the photoreceptors of normal and rd1 mice. Cell and tissue research 26 15789220
2019 Development of a Pde6b Gene Knockout Rat Model for Studies of Degenerative Retinal Diseases. Investigative ophthalmology & visual science 25 31009522
2014 Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice. Molecular vision 25 25489226
1992 The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa. American journal of human genetics 24 1329504
2014 Utility of B-cell epitopes based peptides of RD1 and RD2 antigens for immunodiagnosis of pulmonary tuberculosis. Diagnostic microbiology and infectious disease 23 24485599
2008 Whole blood assays to identify Th1 cell antigens and peptides encoded by Mycobacterium tuberculosis-specific RD1 genes. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 23 18408395
2021 Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa. International journal of molecular sciences 22 33673512
2019 The GGDEF Domain of the Phosphodiesterase PdeB in Shewanella putrefaciens Mediates Recruitment by the Polar Landmark Protein HubP. Journal of bacteriology 22 30670544
2015 Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice. Molecular vision 22 26283863
2005 rd1 mouse retina shows imbalance in cellular distribution and levels of TIMP-1/MMP-9, TIMP-2/MMP-2 and sulfated glycosaminoglycans. Ophthalmic research 22 16374054
2014 Cyr61 activates retinal cells and prolongs photoreceptor survival in rd1 mouse model of retinitis pigmentosa. Journal of neurochemistry 21 24593181
2015 Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions. Scientific reports 20 26602835
2023 Alleviation of Photoreceptor Degeneration Based on Fullerenols in rd1 Mice by Reversing Mitochondrial Dysfunction via Modulation of Mitochondrial DNA Transcription and Leakage. Small (Weinheim an der Bergstrasse, Germany) 19 37407519
2006 An in-house RD1-based enzyme-linked immunospot-gamma interferon assay instead of the tuberculin skin test for diagnosis of latent Mycobacterium tuberculosis infection. Journal of clinical microbiology 19 16757583
2006 Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse. Experimental eye research 19 17069800
2019 Spatio-temporal characterization of S- and M/L-cone degeneration in the Rd1 mouse model of retinitis pigmentosa. BMC neuroscience 18 31481030
2017 Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia. Oncotarget 18 28404878
2008 rd1 Mouse retina shows an imbalance in the activity of cysteine protease cathepsins and their endogenous inhibitor cystatin C. Investigative ophthalmology & visual science 18 18326735
2006 Identification of transcriptionally active open reading frames within the RD1 genomic segment of Mycobacterium tuberculosis. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 18 16484842
2003 Human T-cell responses to the RD1-encoded protein TB27.4 (Rv3878) from Mycobacterium tuberculosis. Immunology 17 14632649
2015 Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration (rd1) mice. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 16 25729279
2014 Spontaneous oscillatory activity in rd1 mouse retina is transferred from ON pathway to OFF pathway via glycinergic synapse. Journal of neurophysiology 16 25355966
2007 RD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion. FEMS microbiology letters 16 17610510
2018 Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6b Mouse Model of Retinitis Pigmentosa. BioMed research international 15 30643804
2013 The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation. Pathogens and disease 15 23913588
2008 Enzymatic characteristics of two novel Myxococcus xanthus enzymes, PdeA and PdeB, displaying 3',5'- and 2',3'-cAMP phosphodiesterase, and phosphatase activities. FEBS letters 15 19114044
2019 A novel intronic mutation of PDE6B is a major cause of autosomal recessive retinitis pigmentosa among Caucasus Jews. Molecular vision 14 30820151