title: Mutation of cGMP phosphodiesterase 6alpha'-subunit gene causes progressive degeneration of cone photoreceptors in zebrafish.
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.
authors.affiliation: Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Promotion Corporation, Suzaki 12-2, Uruma, Okinawa 904-2234, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Komori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sagara
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Manabe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hosoya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nojima
authors.forename: Hironori
authors.initials: H
authors.lastname: Wada
authors.forename: Hideomi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Masai
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D055537:Light Signal Transduction; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology* / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014785:Vision, Ocular; D015027:Zebrafish
chemical_list: D054707:Cyclic Nucleotide Phosphodiesterases, Type 6