TSR1突变导致先天性白内障及其在晶状体中的表达

doi:10.16288/j.yczz.19-166

遗传 ›› 2020, Vol. 42 ›› Issue (2): 161-171.doi: 10.16288/j.yczz.19-166

TSR1突变导致先天性白内障及其在晶状体中的表达

于雅洁^1,²(), 邱峰³, 张新安¹()

^1. 沈阳体育学院运动人体科学学院,沈阳 110102
^2. 辽宁省金秋医院,沈阳 110016
^3. 沈阳市第四人民医院,沈阳市眼科医院,沈阳 110031

收稿日期:2019-10-14 修回日期:2020-01-01 出版日期:2020-01-08 发布日期:2020-01-07
基金资助:
国家自然科学基金项目(81572243)

Studies of congenital cataract-related TSR1 mutation and its expression in the lens

Yajie Yu^1,²(), Feng Qiu³, Xin-an Zhang¹()

^1. College of Kinesiology, Shenyang Sport University, Shenyang 110102, China
^2. Liaoning Jinqiu Hospital, Shenyang 110016, China
^3. The 4th People’s Hospital of Shenyang, Shenyang Eye Hhospital, Shenyang 110031, China;

Received:2019-10-14 Revised:2020-01-01 Online:2020-01-08 Published:2020-01-07
Supported by:
the National Natural Science Foundation of China(81572243)

摘要/Abstract

摘要：

先天性白内障(congenital cataract, CC)是一种罕见的晶状体发育异常疾病,主要表现为晶状体部分或完全浑浊。先天性白内障遗传异质性高,已鉴定的致病基因多达266个。本研究在一个中国先天性白内障家系中通过全基因组测序及Sanger测序验证,筛查到一个新的先天性白内障候选致病基因TSR1,与家系疾病表型共分离。通过minigene实验证实该变异影响TSR1基因mRNA剪接。Western blotting、免疫荧光和RT-PCR实验证实TSR1在人晶状体上皮细胞SRA01/04、年龄相关性白内障患者晶状体前囊膜组织、24周人胎眼晶状体和小鼠晶状体中表达。通过对iSyTE数据库的分析发现,Tsr1在小鼠的胚胎期和不同发育时期的晶状体中都有表达,且在晶状体特异性CBP:p300双敲除小鼠中Tsr1表达下调。提取在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(protein-protein interaction,PPI)分析,结果表明筛选出6个基因与Tsr1存在直接相互作用。GO功能分析表明Tsr1参与核糖体的组装,还可能在MAPK-Erk信号通路中发挥作用,为进一步明确Tsr1在晶状体中的功能提供了有价值的研究线索。

关键词: TSR1, 晶状体, 蛋白质相互作用网络

Abstract:

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.

Key words: TSR1, lens, protein-protein interaction

于雅洁, 邱峰, 张新安. TSR1突变导致先天性白内障及其在晶状体中的表达[J]. 遗传, 2020, 42(2): 161-171.

Yajie Yu, Feng Qiu, Xin-an Zhang. Studies of congenital cataract-related TSR1 mutation and its expression in the lens[J]. Hereditas(Beijing), 2020, 42(2): 161-171.

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编号	染色体	基因名	NM号	变异	功能	是否共分离
1	Chr.1	PDE4DIP	NM_001002811	c.A622G:p.T208A	exonic	否
2	Chr.1	ATP1B1	NM_001677	c.464_465insT	UTR3	否
3	Chr.2	C2orf68	NM_001013649	c.243_239delTTTTT	UTR3	否
4	Chr.5	CXCL14	NM_004887	c.110_92delAAAAAAAAAAAAAAAAAAA	UTR3	否
5	Chr.8	ARHGAP39	NM_025251	c.T1352G:p.M451R	exonic	否
6	Chr.10	NCOA4	NM_001145260	c.T22G:p.F8V	exonic	否
7	Chr.12	KDM5A	NM_001042603	c.-12delC	UTR5	否
8	Chr.12	TPCN1	NM_001301214	c.G854C:p.R285T	exonic	否
9	Chr.15	MEF2A	NM_001130928	c.1027_1029del:p.Q352del	exonic	否
10	Chr.17	TSR1	NM_018128	c.202-1G>A	splicing	是
11	Chr.17	ABCA10	NM_080282	c.A1297G:p.K433E	exonic	否
12	Chr.18	TPGS2	NM_001330572	c.G734A:p.S245N	exonic	否
13	Chr.21	TMPRSS15	NM_002772	c.T1509A:p.N503K	exonic	否
14	Chr.22	SEPT3	NM_019106	c.129_130insTGTG	UTR3	否

TSR1突变导致先天性白内障及其在晶状体中的表达

Studies of congenital cataract-related TSR1 mutation and its expression in the lens

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