TY - JOUR
T1 - Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration
AU - Lumayag, Stephen
AU - Haldin, Caroline E.
AU - Corbett, Nicola J.
AU - Wahlin, Karl J.
AU - Cowan, Colleen
AU - Turturro, Sanja
AU - Larsen, Peter E.
AU - Kovacs, Beatrix
AU - Witmer, P. Dane
AU - Valle, David
AU - Zack, Donald J.
AU - Nicholson, Daniel A.
AU - Xu, Shunbin
PY - 2013/2/5
Y1 - 2013/2/5
N2 - 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- 183CGT/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, photoreceptormorphogenesis, and phototransduction, suggesting that the miR-183/96/182 cluster plays important roles in postnatal functional differentiation and synaptic connectivity of photoreceptors.
AB - 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- 183CGT/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, photoreceptormorphogenesis, and phototransduction, suggesting that the miR-183/96/182 cluster plays important roles in postnatal functional differentiation and synaptic connectivity of photoreceptors.
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U2 - 10.1073/pnas.1212655110
DO - 10.1073/pnas.1212655110
M3 - Article
C2 - 23341629
AN - SCOPUS:84873447141
SN - 0027-8424
VL - 110
SP - E507-E516
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -