TY - JOUR T1 - <em>Dicer</em> Inactivation Leads to Progressive Functional and Structural Degeneration of the Mouse Retina JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4878 LP - 4887 DO - 10.1523/JNEUROSCI.0828-08.2008 VL - 28 IS - 19 AU - Devid Damiani AU - John J. Alexander AU - Jason R. O'Rourke AU - Mike McManus AU - Ashutosh P. Jadhav AU - Constance L. Cepko AU - William W. Hauswirth AU - Brian D. Harfe AU - Enrica Strettoi Y1 - 2008/05/07 UR - http://www.jneurosci.org/content/28/19/4878.abstract N2 - 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. ER -