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Cerebellar neurodegeneration in the absence of microRNAs.

TitleCerebellar neurodegeneration in the absence of microRNAs.
Publication TypeJournal Article
Year of Publication2007
AuthorsSchaefer A, O'Carroll D, Tan CLek, Hillman D, Sugimori M, Llinas R, Greengard P
JournalJ Exp Med
Volume204
Issue7
Pagination1553-8
Date Published2007 Jul 9
ISSN0022-1007
KeywordsAnimals, Apoptosis, Cell Differentiation, Cerebellum, Disease Models, Animal, Immunohistochemistry, In Situ Nick-End Labeling, Mice, MicroRNAs, Nerve Degeneration, Purkinje Cells
Abstract

Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell-specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders.

DOI10.1084/jem.20070823
Alternate JournalJ. Exp. Med.
PubMed ID17606634
PubMed Central IDPMC2118654
Grant ListAG 09464 / AG / NIA NIH HHS / United States
DA 10044 / DA / NIDA NIH HHS / United States
MH 074866 / MH / NIMH NIH HHS / United States
NS 13742 / NS / NINDS NIH HHS / United States
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