Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration
Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration
复制标题
DOI：
10.1073/pnas.1212655110
复制
发表时间：
2013-02-05
影响因子：
11.1
通讯作者：
Xu, Shunbin
中科院分区：
文献类型：
--
作者：
Lumayag, Stephen;Haldin, Caroline E.;Xu, Shunbin
microRNA-183/96/182在视网膜和其他感觉器官中高度表达。为了揭示其在视网膜中的体内功能，我们使用基因陷阱胚胎干细胞克隆生成了一个敲除小鼠模型，命名为“miR-183C（GT/GT）”。我们提供的证据表明，该簇的失活导致光感受器的早发性和进行性突触缺陷，导致暗位和光位视网膜电图异常，b波振幅下降作为主要缺陷和进行性视网膜变性。此外，miR-183/96/182簇的失活导致视网膜基因表达的全局变化，突触发生、突触传递、光感受器形态发生和光转导等重要基因的富集，表明miR-183/96/182簇在出生后光感受器的功能分化和突触连接中起重要作用。
The microRNA-183/96/182 cluster is highly expressed in the retina and other sensory organs. To uncover its in vivo functions in the retina, we generated a knockout mouse model, designated "miR-183C(GT/GT)," using a gene-trap embryonic stem cell clone. We provide evidence that inactivation of the cluster results in early-onset and progressive synaptic defects of the photoreceptors, leading to abnormalities of scotopic and photopic electroretinograms with decreased b-wave amplitude as the primary defect and progressive retinal degeneration. In addition, inactivation of the miR-183/96/182 cluster resulted in global changes in retinal gene expression, with enrichment of genes important for synaptogenesis, synaptic transmission, photoreceptor morphogenesis, and phototransduction, suggesting that the miR-183/96/182 cluster plays important roles in postnatal functional differentiation and synaptic connectivity of photoreceptors.