Yu Ya-Jie, Qiu Feng, Zhang Xin-An
College of Kinesiology, Shenyang Sport University, Shenyang 110102, China; Liaoning Jinqiu Hospital, Shenyang 110016, China.
The 4th People's Hospital of Shenyang, Shenyang Eye Hhospital, Shenyang 110031, China.
Yi Chuan. 2020 Feb 20;42(2):161-171. doi: 10.16288/j.yczz.19-166.
Congenital cataract (CC) is a rare disease with dysplasia of the lens, mainly characterized by partial or complete opacity of the lens. The molecular basis of the disease is complex, mutations in over 266 genes associated with congenital cataracts had been reported. In this study, a novel congenital cataract candidate gene TSR1 was identified by whole genome sequencing and Sanger sequencing in a Chinese congenital cataract family. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA was confirmed by a minigene assay. The expression of TSR1 in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens were determined by RT-PCR, Western blotting, and immunofluorescence assays. The expression of TSR1 in the embryonic and different developmental stages of the mouse lens was confirmed by analyzing the iSyTE database. The expression of TSR1 was down-regulated in the lens-specific CBP:p300 double knockout mouse, and a set of genes with the same expression pattern of Tsr1 in the CBP:p300 double knockout mouse lens were extracted for protein-protein interaction network analysis, and six proteins were screened for direct interaction with Tsr1. GO function analysis indicated that Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to its involvement in ribosome assembly. This study provided valuable research clues to further clarify the function of Tsr1 in the lens.
先天性白内障（CC）是一种晶状体发育异常的罕见疾病，主要特征为晶状体部分或完全混浊。该疾病的分子基础较为复杂，已报道有超过266个与先天性白内障相关的基因发生突变。在本研究中，通过全基因组测序和桑格测序，在中国一个先天性白内障家系中鉴定出一个新的先天性白内障候选基因TSR1。通过小基因检测证实TSR1 c.202-1G>A替换影响了TSR1 mRNA的剪接。通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫荧光检测，确定了TSR1在小鼠晶状体、年龄相关性白内障患者的晶状体前囊以及24周龄人胎儿晶状体中的表达情况。通过分析iSyTE数据库，证实了TSR1在小鼠晶状体胚胎期及不同发育阶段的表达。在晶状体特异性CBP:p300双敲除小鼠中，TSR1的表达下调，提取了CBP:p300双敲除小鼠晶状体中与Tsr1具有相同表达模式的一组基因进行蛋白质-蛋白质相互作用网络分析，筛选出六种与Tsr1直接相互作用的蛋白质。基因本体（GO）功能分析表明，Tsr1除参与核糖体组装外，可能还在丝裂原活化蛋白激酶-细胞外信号调节激酶（MAPK-Erk）信号通路中发挥作用。本研究为进一步阐明Tsr1在晶状体中的功能提供了有价值的研究线索。
