Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration

被引：160
|
作者：
Lumayag, Stephen [1 ,2 ,3 ]
Haldin, Caroline E. [1 ,2 ,3 ]
Corbett, Nicola J. [3 ]
Wahlin, Karl J. [4 ]
Cowan, Colleen [1 ,2 ,3 ]
Turturro, Sanja [1 ,2 ,3 ]
Larsen, Peter E. [5 ]
Kovacs, Beatrix [1 ,2 ,3 ]
Witmer, P. Dane [6 ]
Valle, David [6 ]
Zack, Donald J. [4 ]
Nicholson, Daniel A. [3 ]
Xu, Shunbin [1 ,2 ,3 ]
机构：
[1] Rush Univ, Med Ctr, Dept Pharmacol, Chicago, IL 60612 USA
[2] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA
[3] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA
[4] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA
[5] Argonne Natl Lab, Biosci Div, Lemont, IL 60439 USA
[6] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 06期
关键词：
STATIONARY NIGHT BLINDNESS; DEVELOPING MOUSE RETINA; PROGRESSIVE HEARING-LOSS; CIRCADIAN CLOCK GENE; EMBRYONIC STEM-CELLS; CLASS-I MHC; CONE PHOTORECEPTORS; FUNCTIONAL-ANALYSIS; ALZHEIMERS-DISEASE; DENDRITIC SPINES;
D O I：
10.1073/pnas.1212655110
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
引用
收藏
页码：E507 / E516
页数：10
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