Article

Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.

Department of Microbiology and Immunology, Diabetes Center, Biomedical Sciences Graduate Program, and Departments of Ophthalmology and Physiology, University of California, San Francisco, CA 94122-0534, USA.
Proceedings of the National Academy of Sciences (impact factor: 9.68). 05/2008; 105(14):5614-9. DOI:10.1073/pnas.0801689105 pp.5614-9
Source: PubMed

ABSTRACT MicroRNAs (miRNAs) are small noncoding RNAs that can act to repress target mRNAs by suppressing translation and/or reducing mRNA stability. Although it is clear that miRNAs and Dicer, an RNase III enzyme that is central to the production of mature miRNAs, have a role in the early development of neurons, their roles in the postmitotic neuron in vivo are largely unknown. To determine the roles of Dicer in neurons, we ablated Dicer in dopaminoceptive neurons. Mice that have lost Dicer in these cells display a range of phenotypes including ataxia, front and hind limb clasping, reduced brain size, and smaller neurons. Surprisingly, dopaminoceptive neurons without Dicer survive over the life of the animal. The lack of profound cell death contrasts with other mouse models in which Dicer has been ablated. These studies highlight the complicated nature of Dicer ablation in the brain and provide a useful mouse model for studying dopaminoceptive neuron function.

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Keywords

ataxia
 
brain size
 
complicated nature
 
dopaminoceptive neuron function
 
hind limb clasping
 
mature miRNAs
 
Mice
 
MicroRNAs
 
miRNAs
 
mouse models
 
postmitotic neuron
 
profound cell death contrasts
 
repress target mRNAs
 
RNase III enzyme
 
roles
 
smaller neurons
 
suppressing translation
 
useful mouse model