PUBLICATION

The Ciliopathy Gene ahi1 Is Required for Zebrafish Cone Photoreceptor Outer Segment Morphogenesis and Survival

Authors
Lessieur, E.M., Fogerty, J., Gaivin, R.J., Song, P., Perkins, B.D.
ID
ZDB-PUB-170125-1
Date
2017
Source
Investigative ophthalmology & visual science   58: 448-460 (Journal)
Registered Authors
Fogerty, Joseph, Gaivin, Bob, Lessieur, Emma, Perkins, Brian, Song, Ping
Keywords
none
MeSH Terms
  • Microscopy, Electron, Transmission
  • Mutation*
  • DNA Mutational Analysis
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Retinal Photoreceptor Cell Outer Segment/metabolism
  • Retinal Photoreceptor Cell Outer Segment/ultrastructure*
  • Ciliopathies/genetics*
  • Ciliopathies/metabolism
  • Ciliopathies/pathology
  • Animals
  • Immunohistochemistry
  • Zebrafish
  • Carrier Proteins/genetics*
  • Carrier Proteins/metabolism
  • Cilia/metabolism
  • Cilia/ultrastructure*
  • Genotype
  • Cell Survival
  • Morphogenesis*
  • In Situ Hybridization
  • Proto-Oncogene Proteins
(all 22)
PubMed
28118669 Full text @ Invest. Ophthalmol. Vis. Sci.
Abstract
Joubert syndrome (JBTS) is an autosomal recessive ciliopathy with considerable phenotypic variability. In addition to central nervous system abnormalities, a subset of JBTS patients exhibit retinal dystrophy and/or kidney disease. Mutations in the AHI1 gene are causative for approximately 10% of all JBTS cases. The purpose of this study was to generate ahi1 mutant alleles in zebrafish and to characterize the retinal phenotypes.
Zebrafish ahi1 mutants were generated using transcription activator-like effector nucleases (TALENs). Expression analysis was performed by whole-mount in situ hybridization. Anatomic and molecular characterization of photoreceptors was investigated by histology, electron microscopy, and immunohistochemistry. The optokinetic response (OKR) behavior assay was used to assess visual function. Kidney cilia were evaluated by whole-mount immunostaining.
The ahi1lri46 mutation in zebrafish resulted in shorter cone outer segments but did not affect visual behavior at 5 days after fertilization (dpf). No defects in rod morphology or rhodopsin localization were observed at 5 dpf. By 5 months of age, cone degeneration and rhodopsin mislocalization in rod photoreceptors was observed. The connecting cilium formed normally and Cc2d2a and Cep290 localized properly. Distal pronephric duct cilia were absent in mutant fish; however, only 9% of ahi1 mutants had kidney cysts by 5 dpf, suggesting that the pronephros remained largely functional.
The results indicate that Ahi1 is required for photoreceptor disc morphogenesis and outer segment maintenance in zebrafish.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cu6TgTransgenic Insertion
    lri46
      Small Deletion
      lri47
        Indel
        lri53
          Small Deletion
          1 - 4 of 4
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          Human Disease / Model
          Human Disease Fish Conditions Evidence
          Joubert syndromeahi1lri46/lri46standard conditionsTAS
          1 - 1 of 1
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          Sequence Targeting Reagents
          Target Reagent Reagent Type
          ahi1TALEN1-ahi1TALEN
          1 - 1 of 1
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          Fish
          1 - 4 of 4
          Show
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
          Show
          Mapping
          No data available