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Series GSE28589 Query DataSets for GSE28589
Status Public on May 10, 2011
Title Deletion of astroglial Dicer causes cell non-autonomous neuronal dysfunction and degeneration
Organism Mus musculus
Experiment type Expression profiling by array
Summary The endoribonuclease, Dicer, is indispensible for generating the majority of mature microRNAs (miRNAs), which are posttranscriptional regulators of gene expression involved in a wide range of developmental and pathological processes in mammalian central nervous system. While functions of Dicer-dependent miRNA pathways in neurons and oligodendrocytes have been extensively investigated, little is known about the role of Dicer in astrocytes. Here we report the effect of Cre-loxP mediated conditional deletion of Dicer selectively from postnatal astroglia on brain development. Dicer-deficient mice exhibited normal motor development and neurological morphology prior to postnatal week 5. Thereafter mutant mice invariably developed a rapidly fulminant neurological decline characterized by ataxia, severe progressive cerebellar degeneration, seizures, uncontrollable movements and premature death by postnatal week 9-10. Integrated transcription profiling, histological and functional analyses of cerebella showed that deletion of Dicer in cerebellar astrocytes altered the transcriptome of astrocytes to be more similar to an immature or reactive-like state prior to the onset of neurological symptoms or morphological changes. As a result, critical and mature astrocytic functions including glutamate uptake and antioxidant pathways were substantially impaired, leading to massive apoptosis of cerebellar granule cells and degeneration of Purkinje cells. Collectively, our study demonstrates the critical involvement of Dicer in normal astrocyte maturation and maintenance. Our findings also reveal non-cell autonomous roles of astrocytic Dicer-dependent pathways in regulating proper neuronal functions and implicate that loss of or dysregulation of astrocytic Dicer-dependent pathways may be involved in neurodegeneration and other neurological disorders.
 
Overall design Four replicate experiments using samples derived from biologically independent pairs of control (mGfap-Cre; Dicer +/flox) and Dicer mutant (mGfap-Cre; Dicer flox/flox) littermate mice (postnatal day 30) were performed with a dye-swap experimental design.
 
Contributor(s) Tao J, Wu H, Sun YE
Citation(s) 21632951
Submission date Apr 13, 2011
Last update date May 10, 2018
Contact name Yi Sun
E-mail(s) ysun@mednet.ucla.edu
Phone 310-825-9506
Organization name UCLA
Department Molecular and Medical Pharmacology
Street address 635, Charles E. Young Dr. South
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL4134 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version)
Samples (4)
GSM707668 Control vs Dicer mutant cerebellum, Replicate 1
GSM707669 Control vs Dicer mutant cerebellum, Replicate 2
GSM707670 Control vs Dicer mutant cerebellum, Replicate 3
Relations
BioProject PRJNA139117

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE28589_RAW.tar 69.6 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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