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

Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E507-16. doi: 10.1073/pnas.1212655110. Epub 2013 Jan 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Introns
  • Light / adverse effects
  • Mice
  • Mice, Knockout
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Multigene Family
  • Neurogenesis / genetics
  • Photoreceptor Cells, Vertebrate / metabolism
  • Retina / injuries
  • Retina / metabolism
  • Retina / radiation effects
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / pathology
  • Retinal Degeneration / physiopathology
  • Sense Organs / metabolism
  • Synapses / genetics
  • Synapses / metabolism
  • Synaptic Transmission / genetics
  • Syndrome
  • Vision, Ocular / genetics

Substances

  • MicroRNAs
  • Mirn182 microRNA, mouse
  • Mirn183 microRNA, mouse
  • Mirn96 microRNA, mouse

Associated data

  • GENBANK/KC408930
  • GENBANK/KC408931