ZFIN ID: ZDB-PUB-100309-25
The Intraflagellar Transport Protein Ift80 is essential for Photoreceptor Survival in a Zebrafish Model of Jeune Asphyxiating Thoracic Dystrophy
Hudak, L.M., Lunt, S., Chang, C.H., Winkler, E., Flammer, H., Lindsey, M., and Perkins, B.
Date: 2010
Source: Investigative ophthalmology & visual science   51(7): 3792-3799 (Journal)
Registered Authors: Perkins, Brian
Keywords: outer segments, photoreceptor morphology, retinal degeneration
MeSH Terms:
  • Animals
  • Asphyxia/genetics
  • Asphyxia/pathology*
  • Blotting, Western
  • Carrier Proteins/physiology*
  • Cell Survival/physiology
  • Disease Models, Animal*
  • Electrophoresis, Polyacrylamide Gel
  • Exostoses, Multiple Hereditary/genetics
  • Exostoses, Multiple Hereditary/pathology*
  • Fluorescent Antibody Technique, Indirect
  • Gene Silencing/drug effects
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Kidney Diseases, Cystic/genetics
  • Kidney Diseases, Cystic/pathology
  • Photoreceptor Cells, Vertebrate/pathology*
  • Retinal Degeneration/genetics
  • Retinal Degeneration/pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thoracic Diseases/genetics
  • Thoracic Diseases/pathology*
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed: 20207966 Full text @ Invest. Ophthalmol. Vis. Sci.
Purpose: Jeune's Asphyxiating Thoracic Dystrophy (JATD) is an autosomal recessive disorder with symptoms of retinal degeneration, kidney cysts, and chondrodysplasia and results from mutations in the ift80 gene. This study was conducted to characterize zebrafish lacking ift80 function for photoreceptor degeneration and defects in ciliogenesis in order to establish zebrafish as a vertebrate model for visual dysfunction in JATD and to determine if ift80 interacts genetically with Bardet-Biedl Syndrome (BBS) genes. Methods: Zebrafish were injected with morpholinos (MOs) targeted to the ift80 gene. Retinas were analyzed by histology, transmission electron microscopy, and immunohistochemistry. Ear and kidney cilia were analyzed by whole-mount immunostaining. Intraflagellar Transport (IFT) particle composition was analyzed by Western blotting. Genetic interactions were tested by co-injection of MOs against ift80 and bbs4 or bbs8 followed by in situ hybridization. Results: Zebrafish lacking ift80 function exhibited defects in photoreceptor outer segment formation, and photoreceptor death. Staining with opsin antibodies revealed opsin mislocalization in both rods and cones. Ultrastructural analysis showed abnormal disk stacking and shortened photoreceptor outer segments. The kinocilia of the ear and motile cilia in the kidney were shorter and reduced in number. Western blotting revealed a slight increase in the stability of other IFT proteins. Co-injection of MOs against ift80 and BBS genes led to convergent-extension defects. Conclusions: Zebrafish lacking ift80 exhibited defects characteristic of Jeune's Asphyxiating Thoracic Dystrophy. Because the developing outer segments degenerated, Ift80 could possibly act as a maintenance factor for the IFT particle.