Nusinowitz Steven, Nguyen Lina, Radu Roxanna, Kashani Zahra, Farber Debora, Danciger Michael
Jules Stein Eye Institute, UCLA Medical Center, 100 Stein Plaza, Los Angeles, CA 90095, USA.
Exp Eye Res. 2003 Nov;77(5):627-38. doi: 10.1016/s0014-4835(03)00217-3.
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.
我们的目的是研究在第450位氨基酸编码甲硫氨酸或亮氨酸的Rpe65基因发生变异的白化小鼠的生理表型。从具有MET450的C57BL/6J-c(2J)白化小鼠和具有LEU450的BALB/cByJ白化小鼠记录全视野视网膜电图（ERG）。来自有色小鼠（C57BL/6J）的记录用作对照。用模型拟合视杆ERG a波以估计激活参数。通过监测暗适应视网膜电图的漂白前a波或b波振幅的恢复来研究光漂白后的功能恢复。与有色对照相比，白化小鼠从视杆模型拟合得出的参数S显著更高。在白化小鼠中，与C57BL/6J-c(2J)相比，BALB/cByJ的S最高。参数t(d)和Rm(P3)在这三个品系中没有差异。BALB/cByJ和C57BL/6J-c(2J)白化品系之间S的差异被解释为反映了内在光转导增益的差异。与BALB/cByJ白化小鼠相比，C57BL/6J-c(2J)白化小鼠从光漂白中恢复也更慢，这与先前的研究一致，该研究表明具有RPE65-METH450变体的小鼠视紫红质再生减慢。ERG记录表明，具有RPE65蛋白MET450变体的C57BL/6J-c(2J)白化小鼠比具有LEU450的BALB/cByJ白化小鼠具有更低的激活增益和更慢的光漂白恢复。C57BL/6J-c(2J)品系光漂白恢复较慢和激活增益较低的特征都可能有助于其相对于BALB/c免受光诱导的光感受器死亡的机制。
