The retinas from Period 1 (Per1) and Period 2 (Per2) double-mutant mice (Per1^−/− Per2^Brdm1) display abnormal blue-cone distribution associated with a reduction in cone opsin mRNA and protein levels, up to 1 year of age. To reveal the molecular mechanisms by which Per1 and Per2 control retina development, we analyzed genome-wide gene expression differences between wild-type (WT) and Per1^−/− Per2^Brdm1 mice across ocular developmental stages (E15, E18 and P3). All clock genes displayed changes in transcript levels along with normal eye development. RNA-Seq data show major gene expression changes between WT and mutant eyes, with the number of differentially expressed genes (DEG) increasing with developmental age. Functional annotation of the genes showed that the most significant changes in expression levels in mutant mice involve molecular pathways relating to circadian rhythm signaling at E15 and E18. At P3, the visual cascade and the cell cycle were respectively higher and lower expressed compared to WT eyes. Overall, our study provides new insights into signaling pathways -phototransduction and cell cycle- controlled by the circadian clock in the eye during development.

第1期（Per1）和第2期（Per2）双突变小鼠（Per1 ^-/- Per2 ^Brdm1）的^视网膜显示异常的蓝锥分布，与视锥蛋白mRNA和蛋白质水平的降低相关，直至1岁。为了揭示Per1和Per2控制视网膜发育的分子机制，我们分析了野生型（WT）和Per1 ^-/- Per2 ^Brdm1之间的全基因组基因表达差异小鼠处于眼部发育阶段（E15，E18和P3）。所有的时钟基因都显示出转录水平的变化以及正常的眼睛发育。RNA-Seq数据显示了野生型和突变型眼之间的主要基因表达变化，差异表达基因（DEG）的数量随着年龄的增长而增加。基因的功能注释显示，突变小鼠中表达水平最显着的变化涉及与E15和E18的昼夜节律信号有关的分子途径。在P3，与WT眼睛相比，视觉级联和细胞周期分别更高和更低表达。总体而言，我们的研究为发育过程中由昼夜节律控制的信号传导途径-光转导和细胞周期提供了新见解。