PURPOSE Homozygous inactivation of the mouse gene for GRK1 (G protein-coupled receptor kinase 1, or rhodopsin kinase) causes severe defects in the recovery of cone phototransduction. However, electroretinographic (ERG) analyses of human oguchi patients with defective GRK1 alleles showed normal or slightly abnormal photopic responses. It remains unclear why the loss of GRK1 yields such different...

PURPOSE To determine whether constitutive signal flow arising from defective rhodopsin shut-off causes photoreceptor cell death in arrestin knockout mice. METHODS The retinas of cyclic-light-reared, pigmented arrestin knockout mice and wild-type littermate control mice were examined histologically for photoreceptor cell loss from 100 days to 1 year of age. In separate experiments, to determin...

Jin Nakamura, Tamio Oguchi, Nobuyoshi Yamada, Kazuhiko Kuroki, Kozo Okada, Yoshihiko Takano, Masanori Nagao, Isao Sakaguchi, Hiroshi Kawarada, Rupert C.C. Perera, and David L. Ederer Department of Applied Physics & Chemistry, The University of Electro-Communications, Chofu, Tokyo 182-8585, Japan Department of Quantum Matter, ADSM, Hiroshima University, Higashihiroshima, Hiroshima 739-8530, Japa...

PURPOSE To evaluate proton magnetic resonance spectroscopy ((1)H-MRS) in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B) to obtain binocula...

Little is known about the molecular mechanism of Schiff base hydrolysis in rhodopsin. We report here our investigation into this process focusing on the role of amino acids involved in a hydrogen bond network around the retinal Schiff base. We find conservative mutations in this network (T94I, E113Q, S186A, E181Q, Y192F, and Y268F) increase the activation energy (E(a)) and abolish the concave A...

Leopard complex spotting is inherited by the incompletely dominant locus, LP, which also causes congenital stationary night blindness in homozygous horses. We investigated an associated single nucleotide polymorphism in the TRPM1 gene in 96 archaeological bones from 31 localities from Late Pleistocene (approx. 17 000 YBP) to medieval times. The first genetic evidence of LP spotting in Europe da...

The G90D rhodopsin mutation is known to produce congenital night blindness in humans. This mutation produces a similar condition in mice, because rods of animals heterozygous (D+) or homozygous (D+/+) for this mutation have decreased dark current and sensitivity, reduced Ca(2+), and accelerated values of tau(REC) and tau(D), similar to light-adapted wild-type (WT) rods. Our experiments indicate...

In the G-protein-coupled receptor phototransduction cascade, visual Arrestin 1 (Arr1) binds to and deactivates phosphorylated light-activated opsins, a process that is critical for effective recovery and normal vision. In this report, we discovered a novel synaptic interaction between Arr1 and N-ethylmaleimide-sensitive factor (NSF) that is enhanced in a dark environment when mouse photorecepto...

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the singl...

Rhodopsin kinase (RK), a rod photoreceptor cytosolic enzyme, plays a key role in the normal deactivation and recovery of the photoreceptor after exposure to light. To date, three different mutations in the RK locus have been associated with Oguchi disease, an autosomal recessive form of stationary night blindness in man characterized in part by delayed photoreceptor recovery [Yamamoto, S., Sipp...