The zebrafish cep290^fh297 mutant allele does not affect photoreceptor viability or function

Abstract

Purpose: Mutations in human CEP290 have been implicated in Joubert syndrome, an autosomal recessive ciliopathy characterized by retinal degeneration. The zebrafish cep290^fh297 mutant harbors a Q1210* stop codon that should result in a truncated protein. The purpose of this study was to characterize the cep290^fh297 mutant for visual function and retinal degeneration.

Methods: The molecular lesion in the cep290^fh297 mutant was confirmed by sequencing genomic DNA. Visual function in 5 day post fertilization (dpf) larvae was assessed by the optokinetic response (OKR) using the VisioTracker. Photoreceptor anatomy and degeneration was investigated using immunohistochemistry for rod, cone, and cilia markers on animals between 5 - 60 dpf.

Results: The cep290^fh297 zebrafish mutants harbors a Q1210* stop codon but does not cause early lethality. At 5 dpf homozygous cep290^fh297 mutants had normal OKR function. The cep290^fh297 homozygous mutants did not show structural alterations in photoreceptors at either 5 dpf or 60 dpf by immunohistochemistry.

Conclusions: The zebrafish cep290^fh297 mutant is a nonsense allele that does not result in early lethality and does not affect visual behavior. Photoreceptor structure was also normal by immunohistochemistry. No photoreceptor degeneration was observed.