Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.
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.
Cuellar
Trinna L
TL
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.
Davis
Tigwa H
TH
Nelson
Peter T
PT
Loeb
Gabriel B
GB
Harfe
Brian D
BD
Ullian
Erik
E
McManus
Michael T
MT
D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000166:cytology*; D053487:DEAD-box RNA Helicases / Q000172:deficiency*; D004195:Disease Models, Animal; D004298:Dopamine; D004722:Endoribonucleases / Q000172:deficiency*; D051379:Mice; D009410:Nerve Degeneration; D009445:Neuroanatomy; D009474:Neurons; D010641:Phenotype; D043244:Ribonuclease III
D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D004298:Dopamine