Disruption of Rest Leads to the Early Onset of Cataracts with the Aberrant Terminal Differentiation of Lens Fiber Cells.
Disruption of Rest Leads to the Early Onset of Cataracts with the Aberrant Terminal Differentiation of Lens Fiber Cells.
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静止的破坏导致白内障的早期发作，并具有异常的晶状体纤维细胞末端分化。
DOI：
10.1371/journal.pone.0163042
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kunisada T
中科院分区：
文献类型：
--
作者：
Aoki H;Ogino H;Tomita H;Hara A;Kunisada T
REST(Re1沉默转录因子，又称Nrsf)通过阻止神经元基因的早熟表达，在体外参与维持神经干/祖细胞的未分化状态。然后，REST在发育中的神经元中的表达减少，以下调使其成熟的神经元基因。然而，由于常规REST基因敲除小鼠的早期胚胎致死表型，REST在体内神经发生过程中的作用仍有待阐明。为了研究休息在眼组织中的作用，我们培育并检测了引起基因消融的小鼠，以特异性地针对包括眼组织在内的神经组织进行休息。我们使用Sox1-Cre等位基因在包括晶状体和视网膜原基在内的早期神经组织中切除了FLOX1 REST基因。由此产生的静息条件基因敲除(CKO)小鼠和对照小鼠被用于比较形态、组织学和基因表达分析。静息CKO小鼠出生后晶状体形态发生异常。晶状体上皮细胞的增殖可能略有减少，并形成空泡，但未见明显的凋亡细胞增加。虽然没有检测到迟发性白内障标志物蛋白的异常表达，但Notch信号相关基因的表达在出生前后上调，随后是晶状体纤维调节因子c-Maf和Prox1的表达下调。REST CKO在出生后立即诱导出一种独特的白内障表型。Notch信号增强和晶状体纤维调节基因表达下调可能是导致这种表型的原因。我们的结果强调了静止功能在晶状体纤维形成中的重要性，这对于维持完整的晶状体结构是必要的。
REST (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. REST expression was then decreased in developing neurons to down-regulate neuronal genes which allow their maturation. However, the function of REST during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In order to investigate the role of REST in ocular tissues, we generated and examined the mice evoking genetic ablation to Rest specifically to neural tissues including ocular tissue. We used a Sox1-Cre allele to excise the floxed Rest gene in the early neural tissues including the lens and retinal primordia. The resulting Rest conditional knockout (CKO) and co cntrol mice were used in comparative morphological, histological, and gene expression analyses. Rest CKO mice had an abnormal lens morphology after birth. The proliferation of lens epithelial cells was likely to be slightly reduced, and vacuoles formed without a visible increase in apoptotic cells. Although the aberrant expression of late onset cataract marker proteins was not detected, the expression of Notch signaling-related genes including a previously identified REST-target gene was up-regulated around birth, and this was followed by the down-regulated expression of lens fiber regulators such as c-Maf and Prox1. Rest CKO induces a unique cataract phenotype just after birth. Augmented Notch signaling and the down-regulated expression of lens fiber regulator genes may be responsible for this phenotype. Our results highlight the significance of REST function in lens fiber formation, which is necessary for maintaining an intact lens structure.
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影响因子：
3.7
作者：
Abrajano JJ;Qureshi IA;Gokhan S;Zheng D;Bergman A;Mehler MF
通讯作者：
Mehler MF
DOI：
10.1083/jcb.200908048
发表时间：
2010-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kohyama J;Sanosaka T;Tokunaga A;Takatsuka E;Tsujimura K;Okano H;Nakashima K
通讯作者：
Nakashima K
DOI：
10.1073/pnas.0401827101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Bruce, AW;Donaldson, IJ;Buckley, NJ
通讯作者：
Buckley, NJ
影响因子：
64.5
作者：
CHONG, JHA;TAPIARAMIREZ, J;MANDEL, G
通讯作者：
MANDEL, G
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G