Campla Christie K, Breit Hannah, Dong Lijin, Gumerson Jessica D, Roger Jerome E, Swaroop Anand
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA.
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Biol Open. 2017 Jun 15;6(6):881-890. doi: 10.1242/bio.024679.
Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse gene, which resulted in complete loss of the Pias3 protein. mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P)21 retina, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S-opsin expression in the M-cone dominant dorsal retina suggested altered distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month-old retina revealed aberrant expression of a subset of photoreceptor genes. Our studies demonstrate functional redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific, though limited, role of Pias3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina.
活化信号转导子和转录激活子3的蛋白抑制剂（Pias3）通过对关键视网膜转录因子进行翻译后修饰，参与引导视杆和视锥光感受器的分化。为了研究其在视网膜发育过程中的作用，我们删除了小鼠基因的外显子2 - 5，这导致Pias3蛋白完全缺失。突变小鼠未表现出任何明显的表型，即使在18个月时视网膜分层看起来也正常。我们通过对出生后第21天（P21）的视网膜进行绿光刺激后，用电视网膜图检测到明视觉b波振幅降低，这表明中波长（M）视锥细胞的视觉反应受损。直到7个月时，短波长（S）视锥细胞或视杆光感受器的反应均未出现明显变化。在以M视锥细胞为主的背侧视网膜中，S - 视蛋白表达增加，这表明视锥光感受器的分布发生了改变。对P21和18个月大的突变视网膜进行转录组分析，发现了一部分光感受器基因的异常表达。我们的研究证明了SUMO化相关转录控制机制中的功能冗余，并确定了Pias3在调节小鼠视网膜视锥光感受器亚型的空间模式和最佳功能方面具有特定但有限的作用。
