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Series GSE20646 Query DataSets for GSE20646
Status Public on Apr 01, 2010
Title Identification and validation of the pathways and functions regulated by the ROR alpha1 in skeletal muscle
Organism Mus musculus
Experiment type Expression profiling by array
Summary Identification and validation of the pathways and functions regulated by the orphan nuclear receptor, ROR alpha1, in skeletal muscle

The retinoic acid receptor-related orphan receptor (ROR) alpha has been demonstrated to regulate lipid metabolism. We were interested in the physiologically relevant roles, and pathways regulated by RORalpha1 action in skeletal muscle. This major mass organ accounts for ~40% of the total body mass, and significant levels of lipid catabolism, glucose disposal and energy expenditure. We utilized the strategy of targeted muscle specific expression of a truncated (dominant negative) RORalpha∆DE in transgenic mice, to investigate RORalpha1 signalling (and function) in this peripheral tissue. Expression profiling and pathway analysis indicated that RORalpha regulated genes involved in: (i) lipid and carbohydrate metabolism, cardiovascular and metabolic disease; and (ii) the LXR nuclear receptor signaling pathway and, (iii) the Akt and AMPK signaling cascades. This analysis was extensively validated by rigorous qPCR analysis using TaqMan Low Density Arrays, coupled to rigorous statistical analysis (with Empirical Bayes, and Benjamini-Hochberg). Moreover, westerns and metabolic profiling were utilized to validate the genes, proteins and pathways (lipogenic, Akt, AMPK and fatty acid oxidation) involved in the regulation of metabolism by RORalph1. The identified genes and pathways were in concordance with the demonstration of hyperglycemia, glucose intolerance, attenuated insulin stimulated phosphorylation of Akt, and impaired glucose uptake in the transgenic heterozygous Tg-RORalpha∆DE animals. In conclusion, we propose that RORalpha1 is involved in regulating the Akt2-AMPK signalling pathways in the context of lipid homeostasis in skeletal muscle.
 
Overall design Total RNA was compared from quadriceps femoris of both transgenic and wild type mice. Transgenic mice contained a truncated version of human RORalpha1 (RORalpha1delDE) where the entire E region and part of the hinge/D region have been removed. This transgene is driven by a skeletal muscle specific human skeletal alpha-actin (HSA) promoter.
 
Contributor(s) Raichur S, Fitzsimmons RL, Myers SA, Pearen MA, Lau P, Eriksson NA, Wang SM, Muscat GE
Citation(s) 20338882
Submission date Mar 05, 2010
Last update date Jan 18, 2013
Contact name Michael Andrew Pearen
E-mail(s) m.pearen@uq.edu.au
Phone +61 7 33462365
Fax +61 7 33462101
Organization name Institute for Molecular Bioscience
Lab Group Muscat
Street address The University of Queensland
City St Lucia
State/province Queensland
ZIP/Postal code 4072
Country Australia
 
Platforms (1)
GPL6105 Illumina mouse-6 v1.1 expression beadchip
Samples (6)
GSM518351 Wild Type, 1
GSM518352 Wild Type, 2
GSM518353 Wild Type, 3
Relations
BioProject PRJNA124869

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
GSE20646_RAW.tar 5.2 Mb (http)(custom) TAR
GSE20646_non-normalized.txt.gz 1.5 Mb (ftp)(http) TXT
Processed data included within Sample table
Raw data are available on Series record
Raw data provided as supplementary file

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