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Series GSE6210 Query DataSets for GSE6210
Status Public on Jan 01, 2007
Title Hypomorphic Mutation in PGC1beta causes mitochondrial dysfunction and liver insulin resistance
Organism Mus musculus
Experiment type Expression profiling by array
Summary PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver.
Keywords: Liver and quadricpes muscle gene expression, WT vs. PGC1beta mutant
 
Overall design Gene expression levels in liver tissue and quadriceps muscle were compared between WT/Control and PGC1beta mutant tissue. Total RNA was extracted from liver and skeletal muscle using RNAeasy kit (Qiagen, Valencia, CA), according to the manufacturer’s instructions. Synthesis of cRNA, hybridization and scanning of the Affymetrix Murine 430 2.0 chip was performed by Dana Farber Cancer Institute Microarray Core Facility. The microarray data was analyzed by Clustering Analysis using the d-Chip software (Li and Wong, 2001).
 
Citation(s) 17141629
Submission date Nov 01, 2006
Last update date Feb 11, 2019
Contact name Michael Huntgeburth
E-mail(s) mhuntgeb@bidmc.harvard.edu
Phone 1-617-667-3043
Organization name Beth Israel Deaconess Medical Center
Department Endocrinology, Diabetes and Metabolism
Lab Prof. Bradford B. Lowell
Street address 99 Brookline Ave.
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (12)
GSM143364 Liver Experiment 3
GSM143367 Liver Control 2
GSM143368 Liver Control 3
Relations
BioProject PRJNA100627

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Supplementary file Size Download File type/resource
GSE6210_RAW.tar 73.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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