title: Electroretinographic evidence for altered phototransduction gain and slowed recovery from photobleaches in albino mice with a MET450 variant in RPE65.
abstract: Our purpose was to investigate the physiological phenotype of albino mice with a variation in the Rpe65 gene encoding either methionine or leucine at amino acid #450. Full-field electroretinograms (ERGs) were recorded from C57BL/6J-c(2J) albino mice with MET450 and BALB/cByJ albino mice with LEU450. Recordings from pigmented mice (C57BL/6J) served as controls. Rod ERG a-waves were fitted with a model to estimate parameters of activation. Recovery of function following a photobleach was studied by monitoring the return to pre-bleach a- or b-wave amplitudes of the dark-adapted electroretinogram. The parameter, S, derived from the fit of the rod model, was significantly higher for albino mice compared to pigmented controls. Between the albino mice, S was highest for BALB/cByJ compared to C57BL/6J-c(2J). The parameters t(d) and Rm(P3) were not different across the three strains. The difference in S between the BALB/cByJ and C57BL/6J-c(2J) albino strains is interpreted to reflect differences in intrinsic phototransduction gain. Recovery from a photobleach was also slower for the C57BL/6J-c(2J) albino mice compared with BALB/cByJ albino mice, consistent with prior studies showing slowed rhodopsin regeneration in mice with the RPE65-METH450 variant. ERG recordings show that C57BL/6J-c(2J) albino mice with the MET450 variant of the RPE65 protein have a lower gain of activation and slower recovery from photobleach than do the BALB/cByJ albino mice with LEU450. Both the slower recovery from photobleach and lower gain of activation characteristic of the C57BL/6J-c(2J) strain may contribute to the mechanism by which it is protected from light-induced photoreceptor death relative to BALB/c.
authors.affiliation: Jules Stein Eye Institute, UCLA Medical Center, 100 Stein Plaza, Los Angeles, CA 90095, USA. nusinowitz@jsei.ucla.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Nusinowitz
authors.forename: Lina
authors.initials: L
authors.lastname: Nguyen
authors.forename: Roxanna
authors.initials: R
authors.lastname: Radu
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kashani
authors.forename: Debora
authors.initials: D
authors.lastname: Farber
authors.forename: Michael
authors.initials: M
authors.lastname: Danciger
mesh_terms: D016117:Albinism, Ocular / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D038761:Photobleaching; D011506:Proteins / Q000235:genetics*; D020127:Recovery of Function; D013045:Species Specificity; D014785:Vision, Ocular / Q000235:genetics* / Q000502:physiology; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase