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E-GEOD-59672

ABSTRACT: Expression data from DOX(doxorubicin) -treated wild type or CHIP knockout C57BL/6J mice at day 5

PROVIDER: E-GEOD-59672 | ExpressionAtlas | 2015-07-29

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-GEOD-59672-analysis-methods.tsv	Tabular
	E-GEOD-59672-atlasExperimentSummary.Rdata	Rdata
	E-GEOD-59672-configuration.xml	Xml
	E-GEOD-59672-percentile-ranks.tsv	Tabular
	E-GEOD-59672.condensed-sdrf.tsv	Tabular

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Project description:Expression data from DOX(doxorubicin) -treated wild type or CHIP knockout C57BL/6J mice at day 5

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Expression data from DOX(doxorubicin) -treated wild type or CHIP knockout C57BL/6J mice at day 5

Project description:The clinical application of doxorubicin as a broad-spectrum anti-tumor antibiotic is limited greatly by its cardiotoxicity. Various mechanisms have been studied, but little is known about whether genes or pathways relevant with energy metabolism contributes to doxorubicin-induced cardiomyopathy or not. We used microarrays to detail the global expression profiling of acute cardiomyopathy induced by doxorubicin in wild type or CHIP knockout C57BL/6J mice and discovered distinct classes of changed genes during this process. The whole hearts were selected for RNA extraction and hybridization on Affymetrix microarrays at day 5 after a single intraperitoneal injection of doxorubicin at a dose of 15 mg/kg.

2014-07-23 | E-GEOD-59672 | biostudies-arrayexpress

Expression data from DOX(doxorubicin) -treated wild type or CHIP knockout C57BL/6J mice at day 5

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Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue.

Project description:OBJECTIVE: Brown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and shows diurnal oscillation in glucose and triglyceride (TG)-derived FA-uptake, peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity.METHODS: RNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing and lipidomics analyses were performed on BAT samples of wild type C57BL/6J mice collected at 3-h intervals throughout the day. Knockout and overexpression models were used to study causal relationships in diurnal lipid handling by BAT.RESULTS: We identified pronounced enrichment of oscillating genes involved in extracellular lipolysis in BAT, accompanied by oscillations of FA and monoacylglycerol content. This coincided with peak lipoprotein lipase (Lpl) expression, and was predicted to be driven by peroxisome proliferator-activated receptor gamma (PPARγ) activity. ChIP-sequencing for PPARγ confirmed oscillation in binding of PPARγ to Lpl. Of the known LPL-modulators, angiopoietin-like 4 (Angptl4) showed the largest diurnal amplitude opposite to Lpl, and both Angptl4 knockout and overexpression attenuated oscillations of LPL activity and TG-derived FA-uptake by BAT.CONCLUSIONS: Our findings highlight involvement of PPARγ and a crucial role of ANGPTL4 in mediating the diurnal oscillation of TG-derived FA-uptake by BAT, and imply that time of day is essential when targeting LPL activity in BAT to improve metabolic health.

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Project description:Genetically engineered mice (GEM) are essential tools for understanding gene function and disease modeling. Due to historical reasons, gene targeting was at first done in embryonic stem cells (ESC) derived from the 129 family of inbred strains, leading to mixed background or congenic mice when crossed with C57BL/6 mice. Depending on the number of backcrosses and breeding strategies genomic segments from 129-derived ESC can be introgressed into the C57BL/6 genome at different levels, establishing a unique genetic makeup that needs characterization in order to obtain valid conclusions of experiments using GEM models. We sequenced wild-type (WT), heterozygous (Het) and knockout (KO) mouse embryonic fibroblasts (MEFs) from a knockout model of Sall2 (Sato A. et al, Zinc finger protein sall2 is not essential for embryonic and kidney development. Mol Cell Biol 2003, 23:62-69) maintained in a mixed background between C57BL/6J and 129P2OlaHsd mice. We also treated these cells with doxorubicin, as a global perturbation of the gene expression. With this schema, we aimed to detect genetic introgression of 129 mice onto C57BL/6J, KO-ligated variants (the so-called congenic footprint) and potential modifier genes.

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