title: Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration.
abstract: 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.
authors: Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA.
authors: Stephen
authors: S
authors: Lumayag
authors: Caroline E
authors: CE
authors: Haldin
authors: Nicola J
authors: NJ
authors: Corbett
authors: Karl J
authors: KJ
authors: Wahlin
authors: Colleen
authors: C
authors: Cowan
authors: Sanja
authors: S
authors: Turturro
authors: Peter E
authors: PE
authors: Larsen
authors: Beatrix
authors: B
authors: Kovacs
authors: P Dane
authors: PD
authors: Witmer
authors: David
authors: D
authors: Valle
authors: Donald J
authors: DJ
authors: Zack
authors: Daniel A
authors: DA
authors: Nicholson
authors: Shunbin
authors: S
authors: Xu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007438:Introns; D008027:Light / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D055495:Neurogenesis / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D012160:Retina / Q000293:injuries / Q000378:metabolism / Q000528:radiation effects; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D012679:Sense Organs / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics; D013577:Syndrome; D014785:Vision, Ocular / Q000235:genetics
chemical_list: D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; C543802:Mirn183 microRNA, mouse; C541554:Mirn96 microRNA, mouse