Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.
Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.
复制标题
AE3氯化物/碳酸氢盐交换器缺乏引起的失明。
DOI：
10.1371/journal.pone.0000839
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发表时间：
2007-09-05
期刊：
影响因子：
3.7
通讯作者：
Sauve, Yves
中科院分区：
文献类型：
--
作者：
Alvarez, Bernardo V.;Gilmour, Gregory S.;Mema, Silvina C.;Martin, Brent T.;Shull, Gary E.;Casey, Joseph R.;Sauve, Yves
视觉是由光感受器在视网膜外部的光传导启动的，光感受器的高代谢率会产生大量的二氧化碳负荷。然后，视网膜内部细胞处理视觉信号和二氧化碳。阴离子交换因子3基因(AE3/SLC4a3)编码全长AE3(AE3f1)和心脏AE3(AE3c)亚型，催化Müler(AE3f1)和水平(AE3c)细胞的质膜Cl−/HCO3−交换。因此，AE3通过去除光感受器产生的二氧化碳废物来维持酸平衡。我们报告了SLC4a3−/−缺失小鼠存在视网膜内部缺陷(视网膜电波b波降低、视神经和视网膜血管异常)。这些病理特征是大多数人类玻璃体视网膜变性的共同特征。免疫印迹分析显示，Na+/HCO3AE3共转运体(Nbc1)、碳酸氢酶II和−IV在SLC4a3−/−小鼠视网膜中的蛋白表达增加，提示AE3的丢失是代偿的。TUNEL染色显示，SLC4a3-−/−小鼠4-6月龄的凋亡细胞核数量增加，表明光感受器迟发性死亡。对SLC4a3的鉴定表明，SLC4a3基因是遗传性玻璃体视网膜变性的一个新的候选基因。
Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl−/HCO3 − exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste. We report that Slc4a3−/− null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3 − co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3 −/− mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4–6 months of age, in Slc4a3 −/− mice, indicating late onset photoreceptor death. Identification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration.
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影响因子：
4.2
作者：
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通讯作者：
EVERETT, WG
影响因子：
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通讯作者：
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通讯作者：
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