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Series GSE10503 Query DataSets for GSE10503
Status Public on May 22, 2008
Title Identification of transcriptional changes due to loss of Hdac3 in liver at P17 and P28
Organism Mus musculus
Experiment type Expression profiling by array
Summary Histone deacetylase 3 (Hdac3) is the enzymatic component of transcriptional repression complexes recruited by the nuclear hormone receptors. Inactivation of Hdac3 in cancer cell lines triggered apoptosis, and removal of Hdac3 in the germ-line of mice caused embryonic lethality. Therefore, we conditionally deleted the Hdac3 allele in the mouse liver. These mice developed hepatomegaly, which was the result of hepatocyte hypertrophy, and these morphological changes coincided with significant imbalances between carbohydrate and lipid metabolism. Loss of Hdac3 triggered changes in gene expression consistent with inactivation of repression mediated by nuclear hormone receptors. Mechanistically, loss of Hdac3 increased the levels of PparĪ³2, and treatment of these mice with a PparĪ³ antagonist partially reversed the lipid accumulation in the liver. In addition, gene expression analysis identified mTOR (mammalian target of rapamycin) signaling as being activated by deletion of Hdac3, and inhibition by rapamycin also affected the accumulation of neutral lipids in the Hdac3-null livers. Thus, Hdac3 has a key role in regulation of multiple signaling pathways in the liver, and deletion of Hdac3 disrupts normal metabolic homeostasis.
Keywords: Genetic knockout of Hdac3 specifically in liver, and RNA analyzed from postnatal day 17 or 28 livers for transcriptional changes related to the given phenotypes
 
Overall design Postnatal day 17 or 28 mice were used for the microarray analysis. Total RNA was extracted from livers of either Hdac3 wild-type/heterozygous mice expressing Albumin-Cre or Hdac3-null livers, and pooled together in groups of 5. One pool of control or Hdac3-null liver RNA from both time points was used in technical replicates, meaning each sample was run in duplicate on separate lots of microarray chips to determine reproducibility of the Applied Biosystems ABI1700 chips. The second set of RNA pools were used as biological replicates for each group at each time point.
 
Contributor(s) Knutson SK, Chyla BI, Amann JM, Bhaskara S, Huppert SS, Hiebert SW
Citation(s) 18354499
Submission date Feb 12, 2008
Last update date Mar 19, 2012
Contact name Sarah K Knutson
Organization name Vanderbilt University
Department Biochemistry
Street address 23rd and Pierce Ave
City Nashville
State/province TN
ZIP/Postal code 37232
Country USA
 
Platforms (1)
GPL2995 ABI Mouse Genome Survey Microarray
Samples (12)
GSM265475 P17 Hdac3 control liver biological replicate
GSM265476 P17 Hdac3 control liver technical replicate 1
GSM265477 P17 Hdac3 control liver technical replicate 2
Relations
BioProject PRJNA107957

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Supplementary file Size Download File type/resource
GSE10503_RAW.tar 24.9 Mb (http)(custom) TAR (of XLS)
Processed data included within Sample table

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