RRC ID 4108
Author Nishiwaki Y, Komori A, Sagara H, Suzuki E, Manabe T, Hosoya T, Nojima Y, Wada H, Tanaka H, Okamoto H, Masai I.
Title Mutation of cGMP phosphodiesterase 6alpha'-subunit gene causes progressive degeneration of cone photoreceptors in zebrafish.
Journal Mech. Dev.
Abstract In mammals, the blockade of the phototransduction cascade causes loss of vision and, in some cases, degeneration of photoreceptors. However, the molecular mechanisms that link phototransduction with photoreceptor degeneration remain to be elucidated. Here, we report that a mutation in the gene encoding a central effector of the phototransduction cascade, cGMP phosphodiesterase 6alpha'-subunit (PDE6alpha'), affects not only the vision but also the survival of cone photoreceptors in zebrafish. We isolated a zebrafish mutant, called eclipse (els), which shows no visual behavior such as optokinetic response (OKR). The cloning of the els mutant gene revealed that a missense mutation occurred in the pde6alpha' gene, resulting in a change in a conserved amino acid. The PDE6 expressed in rod photoreceptors is a heterotetramer comprising two closely related similar hydrolytic alpha and beta subunits and two identical inhibitory gamma subunits, while the PDE6 expressed in cone photoreceptors consists of two homodimers of alpha' subunits, each with gamma subunits. The els mutant displays no visual response to bright light, where cones are active, but shows relatively normal OKR to dim light, where only rods function, suggesting that only the cone-specific phototransduction pathway is disrupted in the els mutant. Furthermore, in the els mutant, cones are selectively eliminated but rods are retained at the adult stage, suggesting that cones undergo a progressive degeneration in the els mutant retinas. Taken together, these data suggest that PDE6alpha' activity is important for the survival of cones in zebrafish.
Volume 125(11-12)
Pages 932-46
Published 2008-11
DOI 10.1016/j.mod.2008.09.001
PII S0925-4773(08)00136-6
PMID 18824093
MeSH Alleles Amino Acid Sequence Animals Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics* Cyclic Nucleotide Phosphodiesterases, Type 6 / physiology Gene Expression Regulation* Humans Light Signal Transduction Molecular Sequence Data Mutation, Missense* Retinal Cone Photoreceptor Cells / pathology* Retinal Cone Photoreceptor Cells / physiology Retinal Degeneration / genetics* Retinal Rod Photoreceptor Cells / pathology Retinal Rod Photoreceptor Cells / physiology Sequence Homology, Amino Acid Vision, Ocular Zebrafish
IF 2.176
Times Cited 13
Zebrafish RIKEN WT (RW)