PUBLICATION

Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish

Authors
Iribarne, M., Nishiwaki, Y., Nakamura, S., Araragi, M., Oguri, E., Masai, I.
ID
ZDB-PUB-170406-7
Date
2017
Source
Scientific Reports   7: 45962 (Journal)
Registered Authors
Araragi, Masato, Iribarne, Maria, Masai, Ichiro, Nishiwaki, Yuko, Oguri, Eri
Keywords
Disease model, Hereditary eye disease, Neurodegeneration, Neurodevelopmental disorders
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Fertilization
  • Retinal Cone Photoreceptor Cells/cytology*
  • Retinal Cone Photoreceptor Cells/metabolism*
  • Phenotype
  • Cell Survival
  • Epistasis, Genetic
  • Protein Transport
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Cyclic GMP/metabolism
  • Guanylate Cyclase/genetics
  • Guanylate Cyclase/metabolism*
  • Subcellular Fractions/metabolism
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 6/metabolism*
  • Mutation/genetics
  • Opsins/metabolism
  • Protein Stability
  • Retinal Degeneration/pathology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 25)
PubMed
28378769 Full text @ Sci. Rep.
Abstract
Genetic mutations in aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) cause photoreceptor degeneration associated with Leber congenital amaurosis 4 (LCA4) in human patients. Here we report retinal phenotypes of a zebrafish aipl1 mutant, gold rush (gosh). In zebrafish, there are two aipl1 genes, aipl1a and aipl1b, which are expressed mainly in rods and cones, respectively. The gosh mutant gene encodes cone-specific aipl1, aipl1b. Cone photoreceptors undergo progressive degeneration in the gosh mutant, indicating that aipl1b is required for cone survival. Furthermore, the cone-specific subunit of cGMP phosphodiesterase 6 (Pde6c) is markedly decreased in the gosh mutant, and the gosh mutation genetically interacts with zebrafish pde6c mutation eclipse (els). These data suggest that Aipl1 is required for Pde6c stability and function. In addition to Pde6c, we found that zebrafish cone-specific guanylate cyclase, zGc3, is also decreased in the gosh and els mutants. Furthermore, zGc3 knockdown embryos showed a marked reduction in Pde6c. These observations illustrate the interdependence of cGMP metabolism regulators between Aipl1, Pde6c, and Gc3 in photoreceptors.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
aipl2oki6/oki6standard conditionsProtruding-mouth
aipl2oki6/oki6standard conditionsDays 45-89
aipl2oki6/oki6standard conditionsDays 45-89
aipl2oki6/oki6standard conditionsDays 45-89
aipl2oki6/oki6standard conditionsDays 45-89
aipl2oki6/oki6standard conditionsDays 45-89
aipl2s341/s341standard conditionsDays 7-13
aipl2s341/s341standard conditionsDays 7-13
aipl2s341/s341standard conditionsDays 7-13
aipl2s341/s341standard conditionsDays 7-13
1 - 10 of 21
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
oki6
    		Insertion
    rw76a
      		Point Mutation
      s341
        		Point Mutation
        w59
          		Point Mutation
          1 - 4 of 4
          Show
          Human Disease / Model
          Human Disease Fish Conditions Evidence
          Leber congenital amaurosis 4aipl2oki6/oki6standard conditionsTAS
          1 - 1 of 1
          Show
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          gucy2dMO1-gucy2dMRPHLNO
          gucy2dMO2-gucy2dMRPHLNO
          aipl2CRISPR1-aipl2CRISPR
          1 - 3 of 3
          Show
          Fish
          Fish
          aipl2oki6/oki6
          aipl2s341/s341
          pde6crw76a/rw76a
          pde6crw76a/rw76a; aipl2oki6/+
          WT
          WT + MO1-gucy2d
          WT + MO2-gucy2d
          1 - 7 of 7
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          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          No data available
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          Citation
          Iribarne, M., Nishiwaki, Y., Nakamura, S., Araragi, M., Oguri, E., Masai, I. (2017) Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish. Scientific Reports. 7:45962.