PUBLICATION

Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish

Authors
Quint, W.H., Tadema, K.C.D., de Vrieze, E., Lukowicz, R.M., Broekman, S., Winkelman, B.H.J., Hoevenaars, M., de Gruiter, H.M., van Wijk, E., Schaeffel, F., Meester-Smoor, M., Miller, A.C., Willemsen, R., Klaver, C.C.W., Iglesias, A.I.
ID
ZDB-PUB-210605-2
Date
2021
Source
Communications biology   4: 676 (Journal)
Registered Authors
de Vrieze, Erik, Iglesias, Adriana, Miller, Adam
Keywords
none
MeSH Terms
  • Humans
  • Retina/metabolism
  • Retina/pathology
  • Refractive Errors/genetics*
  • Connexins/genetics*
  • Connexins/metabolism
  • Mutation*
  • Disease Models, Animal*
  • Cataract/genetics
  • RNA-Seq/methods
  • Animals
  • Myopia/genetics
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Eye Proteins/genetics*
  • Eye Proteins/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Gene Expression Profiling/methods
  • Retinal Pigment Epithelium/metabolism
  • Retinal Pigment Epithelium/pathology
  • Single-Cell Analysis/methods
(all 22)
PubMed
34083742 Full text @ Commun Biol
Abstract
Myopia is the most common developmental disorder of juvenile eyes, and it has become an increasing cause of severe visual impairment. The GJD2 locus has been consistently associated with myopia in multiple independent genome-wide association studies. However, despite the strong genetic evidence, little is known about the functional role of GJD2 in refractive error development. Here, we find that depletion of gjd2a (Cx35.5) or gjd2b (Cx35.1) orthologs in zebrafish, cause changes in the biometry and refractive status of the eye. Our immunohistological and scRNA sequencing studies show that Cx35.5 (gjd2a) is a retinal connexin and its depletion leads to hyperopia and electrophysiological changes in the retina. These findings support a role for Cx35.5 (gjd2a) in the regulation of ocular biometry. Cx35.1 (gjd2b) has previously been identified in the retina, however, we found an additional lenticular role. Lack of Cx35.1 (gjd2b) led to a nuclear cataract that triggered axial elongation. Our results provide functional evidence of a link between gjd2 and refractive error.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsDays 45-89
gjd2afh437/fh437standard conditionsAdult
gjd2afh437/fh437standard conditionsAdult
1 - 10 of 18
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a13203TgTransgenic Insertion
    fh437
      		Small Deletion
      fh454
        		Small Deletion
        mw1
          		Point Mutation
          vu12TgTransgenic Insertion
            1 - 5 of 5
            Show
            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            No data available
            Fish
            Fish
            gjd2afh437/fh437
            gjd2afh437/fh437; gjd2bfh454/fh454
            gjd2bfh454/fh454
            WT
            1 - 4 of 4
            Show
            Antibodies
            Name Type Antigen Genes Isotypes Host Organism
            Ab1-cx35monoclonalIgG1Mouse
            Ab1-gjd2amonoclonalRabbit
            1 - 2 of 2
            Show
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            GCaMPEFGGCaMP
            1 - 2 of 2
            Show
            Mapping
            No data available
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            Citation
            Quint, W.H., Tadema, K.C.D., de Vrieze, E., Lukowicz, R.M., Broekman, S., Winkelman, B.H.J., Hoevenaars, M., de Gruiter, H.M., van Wijk, E., Schaeffel, F., Meester-Smoor, M., Miller, A.C., Willemsen, R., Klaver, C.C.W., Iglesias, A.I. (2021) Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish. Communications biology. 4:676.