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Publication : Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina.

First Author  Damiani D Year  2008
Journal  J Neurosci Volume  28
Issue  19 Pages  4878-87
PubMed ID  18463241 Mgi Jnum  J:135193
Mgi Id  MGI:3790576 Doi  10.1523/JNEUROSCI.0828-08.2008
Citation  Damiani D, et al. (2008) Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 28(19):4878-87
abstractText  MicroRNAs (miRNAs) are small, highly conserved molecules that have been shown to regulate the expression of genes by binding to specific target mRNAs. Dicer, an RNase III endonuclease, is essential for the production and function of mature miRNAs, and removal of Dicer has been shown to disrupt many developmental processes. In this study, Dicer was removed specifically from the retina using a floxed Dicer conditional allele and the retinal Chx10Cre transgene. Retinal Dicer knock-out mice displayed a reproducible inability to respond to light. In addition, morphological defects were observed with the formation of photoreceptor rosettes at postnatal day 16, which progressed to more general cellular disorganization and widespread degeneration of retinal cell types as the animals aged. This was accompanied by concomitant decrease in both scotopic and photopic electroretinogram (ERG) responses. Interestingly, removing a single allele of Dicer resulted in ERG deficits throughout life but not to morphological abnormalities. Northern blot analysis of Dicer-depleted retinas showed a decrease in several miRNAs. The observation that progressive retinal degeneration occurred after removal of Dicer raises the possibility that miRNAs are involved in retinal neurodegenerative disorders.
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