RGD Reference Report - Altered microRNA regulation in Huntington's disease models. - Rat Genome Database

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Altered microRNA regulation in Huntington's disease models.

Authors: Lee, ST  Chu, K  Im, WS  Yoon, HJ  Im, JY  Park, JE  Park, KH  Jung, KH  Lee, SK  Kim, M  Roh, JK 
Citation: Lee ST, etal., Exp Neurol. 2011 Jan;227(1):172-9. doi: 10.1016/j.expneurol.2010.10.012. Epub 2010 Oct 28.
RGD ID: 11041745
Pubmed: PMID:21035445   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2010.10.012   (Journal Full-text)

Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD. However, the profiles and regulation of miRNAs in HD are not fully understood. Here, we analyzed the miRNA expression and miRNA regulators in two transgenic models of HD, YAC128 and R6/2 mice, and in a 3-nitropropionic acid (3NP)-induced striatal degeneration rat model. After characterizing the phenotypes by behavioral tests and histological analyses, we profiled striatal miRNAs using a miRNA microarray and we measured the key molecules involved in miRNA biogenesis and function. YAC128 mice showed upregulation-dominant miRNA expressions at 5 months and downregulation-dominant expressions at 12 months. Concomitantly, the expressions of Drosha-DGCR8, Exportin-5, and Dcp1 were increased at 5months, and the expression of Dicer was decreased at 12 months. In 10-week-old R6/2 mice, downregulation was dominant in the miRNA expressions and the level of Drosha decreased concomitantly. Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice. Meanwhile, 3NP rats showed dynamic changes in the miRNA profiles during disease development and a few miRNAs with altered expression. Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Huntington's disease  ISOMir132 (Mus musculus)11041745; 11041745down-regulatedRGD 
Huntington's disease  ISOMir22 (Mus musculus)11041745; 11041745down-regulatedRGD 
Huntington's disease  ISOMir222 (Mus musculus)11041745; 11041745down-regulatedRGD 
Huntington's disease  ISOMir29c (Mus musculus)11041745down-regulatedRGD 
Huntington's disease  ISOMir448 (Mus musculus)11041745up-regulatedRGD 
Huntington's disease  IEP 11041745; 11041745; 11041745; 11041745down-regulatedRGD 
Huntington's disease  IEP 11041745up-regulatedRGD 
Huntington's disease  ISOXpo5 (Mus musculus)11041745; 11041745mRNA:increased expression:striatum (mouse)RGD 
Huntington's disease  IEP 11041745mRNA:increased expression:striatum (mouse)RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Mir132  (microRNA 132)
Mir22  (microRNA 22)
Mir222  (microRNA 222)
Xpo5  (exportin 5)

Genes (Mus musculus)
Mir132  (microRNA 132)
Mir22  (microRNA 22)
Mir222  (microRNA 222)
Mir29c  (microRNA 29c)
Mir448  (microRNA 448)
Xpo5  (exportin 5)

Genes (Homo sapiens)
MIR132  (microRNA 132)
MIR22  (microRNA 22)
MIR222  (microRNA 222)
MIR29C  (microRNA 29c)
MIR448  (microRNA 448)
XPO5  (exportin 5)


Additional Information