Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.
Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.
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细胞内氯离子通道 CLCC1 突变与常染色体隐性遗传色素性视网膜炎相关
DOI：
10.1371/journal.pgen.1007504
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发表时间：
2018-08
期刊：
影响因子：
4.5
通讯作者：
Hejtmancik JF
中科院分区：
文献类型：
--
作者：
Li L;Jiao X;D'Atri I;Ono F;Nelson R;Chan CC;Nakaya N;Ma Z;Ma Y;Cai X;Zhang L;Lin S;Hameed A;Chioza BA;Hardy H;Arno G;Hull S;Khan MI;Fasham J;Harlalka GV;Michaelides M;Moore AT;Coban Akdemir ZH;Jhangiani S;Lupski JR;Cremers FPM;Qamar R;Salman A;Chilton J;Self J;Ayyagari R;Kabir F;Naeem MA;Ali M;Akram J;Sieving PA;Riazuddin S;Baple EL;Riazuddin SA;Crosby AH;Hejtmancik JF
我们在CLCC 1中发现了一个纯合错义突变（c.75C>A，p.D25E），编码一个假定的视网膜中高度表达的细胞内氯离子通道，与8个巴基斯坦血统的近亲家族中的常染色体隐性视网膜色素变性（arRP）相关。p.D25E改变降低了CLCC 1通道功能，伴随着突变蛋白在ER腔内颗粒中的积累，而CLCC 1 mRNA的siRNA敲低诱导了培养的ARPE-19细胞的凋亡。斑马鱼的TALEN KO在受精后11天是致命的。通过注射野生型CLCC 1 mRNA可以挽救5 dpf KO斑马鱼的降低的视网膜电图（ERG）视锥反应和视锥光谱敏感性以及减小的眼睛大小、视网膜厚度和视杆和视锥视蛋白的表达。Clcc 1 +/- KO小鼠显示ERG和感光细胞数量减少。总之，这些结果强烈表明，通过CLCC 1的细胞内氯离子转运是维持视网膜完整性的关键过程，并且CLCC 1对于视网膜细胞的存活和功能至关重要。
We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p.D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE-19 cells. TALEN KO in zebrafish was lethal 11 days post fertilization. The depressed electroretinogram (ERG) cone response and cone spectral sensitivity of 5 dpf KO zebrafish and reduced eye size, retinal thickness, and expression of rod and cone opsins could be rescued by injection of wild type CLCC1 mRNA. Clcc1+/- KO mice showed decreased ERGs and photoreceptor number. Together these results strongly suggest that intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells.
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影响因子：
1.4
作者：
Marmor, M. F.;Fulton, A. B.;Bach, M.
通讯作者：
Bach, M.
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
9.8
作者：
Li, Lin;Nakaya, Naoki;Hejtmancik, J. Fielding
通讯作者：
Hejtmancik, J. Fielding
DOI：
10.1073/pnas.1019533108
发表时间：
2011-02-08
影响因子：
11.1
作者：
Mahfouz, Magdy M.;Li, Lixin;Zhu, Jian-Kang
通讯作者：
Zhu, Jian-Kang
影响因子：
3.5
作者：
McKie, AB;McHale, JC;Inglehearn, CF
通讯作者：
Inglehearn, CF