A photic visual cycle of rhodopsin regeneration is dependent on Rgr

letter 2001 Nature Publishing Group http://genetics.nature.comA photic visual cycle of rhodopsin regeneration is

dependent on RgrPu Chen1,5, Wenshan Hao2, Lawrence Rife1, Xiao Peng Wang6, Daiwei Shen6, Jeannie Chen3, Thomas Ogden6,

Gretchen B. Van Boemel1,6, Lanyin Wu4, Mao Yang2 & Henry K.W. Fong1,2,6.com2001 Nature Publishing Group http://genetics.natureDuring visual excitation, rhodopsin undergoes photoactivation and bleaches to opsin and all-trans-retinal1,2. To regenerate rhodopsin and maintain normal visual sensitivity, the

all-trans isomer must be metabolized and reisomerized to produce the chromophore 11-cis-retinal in biochemical steps that

constitute the visual cycle and involve the retinal pigment

epithelium (RPE; refs. 38). A key step in the visual cycle is isomerization of an all-trans retinoid to 11-cis-retinol in the RPE

(refs. 911). It could be that the retinochrome-like opsins, peropsin, or the retinal G protein-coupled receptor (RGR)

opsin1216 are isomerases in the RPE. In contrast to visual pigments, RGR is bound predominantly to endogenous all-trans-retinal, and irradiation of RGR in vitro results in stereospecific

conversion of the bound all-trans isomer to 11-cis-retinal17.

Here we show that RGR is involved in the formation of 11-cis-retinal in mice and functions in a light-dependent pathway of

the rod visual cycle. Mutations in the human gene encoding

RGR are associated with retinitis pigmentosa18.We established two independent lines of mice with targeted

disruption of Rgr (Fig. 1). RGR is absent in homozygous Rgr/

mice (Fig. 1c). Despite the presence of only one normal allele in

Rgr+/ mice, the amount of RGR in heterozygotes is equivalent to

that of control Rgr+/+ mice. The levels of rhodopsin protein do

not vary significantly among the mice with different genotypes

(Fig. 1d). The morphological development of the retina appears

normal in Rgr/ mice, and retinal degeneration is not apparent

in 9-month-old mice maintained under cyclic house lighting.To determine the effect of loss of RGR on the amount of retinal

isomers and rhodopsin, we analyzed free-moving Rgr+/+, Rgr+/

and Rgr/ mice that were adapted to a condition of darkness or

constant illumination. In all dark-adapted mice, total retinal is 600

pmol per eye and rhodopsin is 450 pmol per eye (Fig. 2). In each

group of dark-adapted mice, 96% of the total retinal per eye is 11-

cis-retinal; the remainder is the all-trans isomer. There is no significant difference in the amount...