June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
A missense mutation in cep290 causes predominantly cone photoreceptor degeneration in zebrafish (Danio rerio)
Author Affiliations & Notes
  • Wei Zhang
    University of Massachusetts Medical School, Worcester, MA
  • Linjing Li
    University of Massachusetts Medical School, Worcester, MA
  • Hemant Khanna
    University of Massachusetts Medical School, Worcester, MA
  • Footnotes
    Commercial Relationships Wei Zhang, None; Linjing Li, None; Hemant Khanna, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5436. doi:https://doi.org/
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      Wei Zhang, Linjing Li, Hemant Khanna; A missense mutation in cep290 causes predominantly cone photoreceptor degeneration in zebrafish (Danio rerio). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5436. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: CEP290 is a cilia-centrosomal protein involved in regulating cilia formation and function. Mutations in CEP290 are a frequent cause of severe ciliopathies, such as childhood blindness disorder Leber congenital amaurosis (LCA10) as well as multisystem disorders, such as Joubert Syndrome. However, the mechanism by which CEP290 mutations result in heterogenic phenotypes is not clear. We undertook this study to ascertain the pathogenesis associated with a missense mutation in cep290 in zebrafish.

Methods: We obtained cep290 mutant zebrafish from Zebrafish International Resource Center. Polymerase Chain Reaction (PCR) and sequencing were used to validate the mutation. Reverse-Transcription (RT) followed by PCR was performed to evaluate the effect of the mutation on expression of the cep290 gene. Retina, kidney and brain tissues were used for histological, immunofluorescence and electron microscopic (EM) analyses.

Results: We found only one copy of the cep290 gene in zebrafish. Sequence analysis of genomic DNA of cep290 mutants revealed a missense mutation in exon 38 of the cep290 gene. We did not detect any change in the transcription profile of cep290 in the homozygous cep290-mutant zebrafish. The fish survived to adulthood and had normal body structure. No difference was observed in the morphology of kidney and brain between homozygous and control fish. However, we found progressive progressive degeneration of predominantly cone outer segment in homozygous cep290-mutant zebrafish, as early as 2 months. EM analysis revealed disordered cone outer segment with large empty spaces. No effect on rod photoreceptors or other retinal cell types was observed.

Conclusions: Our results show that the observed mutation in cep290 is hypomorphic (partially functional). Its association with a cone-predominant phenotype in zebrafish uncovers a potentially novel role of CEP290 in regulating cone sensory cilia morphology. Further studies are in progress to delineate the mechanism of cone OS degeneration due to cep290 mutation.


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