Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2013 May 1;8(5):e63321. doi: 10.1371/journal.pone.0063321. Print 2013.
The nuclear receptor NR2E3 promotes expression of rod photoreceptor genes while repressing cone genes. Mice lacking NR2E3 (Nr2e3(rd7/rd7) referred to here as rd7) are a model for enhanced S-cone syndrome, a disease associated with increased sensitivity to blue light and night blindness. Rd7 retinas have reduced levels of the outer segment (OS) structural protein retinal degeneration slow (RDS). We test the hypothesis that increasing RDS levels would improve the Rd7 phenotype. Transgenic mice over-expressing normal mouse peripherin/RDS (NMP) in rods and cones were crossed onto the rd7 background. Disease phenotypes were assessed in NMP/rd7 eyes and compared to wild-type (WT) and rd7 eyes at postnatal day 30. NMP/rd7 retinas expressed total RDS (transgenic and endogenous) message at WT levels, and NMP protein was correctly localized to the OS. NMP/rd7 retinas have shorter OSs compared to rd7 and WT and significantly reduced number of rosettes. NMP/rd7 mice also exhibited significant deficits in scotopic ERG amplitudes compared to rd7 while photopic amplitudes remained unaffected. Protein levels of rhodopsin, RDS, and the RDS homologue ROM-1 were significantly reduced in the NMP/rd7 retinas compared to rd7. We show that correcting the levels of RDS gene expression does not improve the phenotype of the rd7 suggesting that RDS deficiency is not responsible for the defect in this model. We suggest that the specific rod defect in the NMP/rd7 is likely associated with ongoing problems in the rd7 that are related to the expression of cone genes in rod cells, a characteristic of the model.
核受体 NR2E3 促进视杆细胞基因的表达，同时抑制视锥细胞基因的表达。缺乏 NR2E3 的小鼠（这里称为 rd7）是增强 S- cone 综合征的模型，该疾病与对蓝光的敏感性增加和夜盲症有关。rd7 视网膜中的外节（OS）结构蛋白视网膜变性慢（RDS）水平降低。我们检验了增加 RDS 水平会改善 rd7 表型的假设。在 rd7 背景下，过表达正常小鼠周边蛋白/RDS（NMP）的转基因小鼠与 rd7 杂交。在 NMP/rd7 眼和 WT 眼以及 rd7 眼的出生后 30 天评估疾病表型，并进行比较。NMP/rd7 视网膜表达的总 RDS（转基因和内源性）mRNA 水平与 WT 相同，并且 NMP 蛋白正确定位于 OS。与 rd7 和 WT 相比，NMP/rd7 视网膜的 OS 更短，rosette 数量显著减少。与 rd7 相比，NMP/rd7 小鼠的暗视 ERG 幅度也显著降低，而明视幅度不受影响。与 rd7 相比，NMP/rd7 视网膜中的视紫红质、RDS 和 RDS 同源物 ROM-1 的蛋白水平显著降低。我们表明，纠正 RDS 基因表达水平并不能改善 rd7 的表型，这表明 RDS 缺乏不是该模型缺陷的原因。我们认为，NMP/rd7 中的特定 rod 缺陷可能与 rd7 中与 rod 细胞中 cone 基因表达有关的持续问题有关，这是该模型的一个特征。
