Early effects of Serum Response Factor (SRF) gene deletion on the vascular gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE34545 | GEO | 2014/12/31
SECONDARY ACCESSION(S): PRJNA151371
REPOSITORIES: GEO
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Project description:The objective of this study is to assess the effects of the Serum Response Factor deletion on the cardiac gene expression program at different time points after the deletion (day 8 and day 25) and to compare the response of SRF-deficient heart and control heart to phenylephrine, an alpha-adrenergic agonist triggering cardiac hypertrophy. To generate cardiomyocyte-specific SRF knockout, 10 week-old mice homozygous for the [SRF-flex2neo] allele bearing one copy of the [alphaMHC-MerCreMer] transgene (SRFHKO mice) (Reference 1) were injected i.p. with 0.7mg of tamoxifen for 3 days. All control (SRF-flex2neo littermates) and SRFHKO mice were systematically injected with tamoxifen to normalize for any effects due to tamoxifen. For the mice treated with phenylephrine (PE), the drug was administrated at 80 mg/kg/day from day 10 to day 25 after the first day of tamoxifen injection, using Alzet osmotic minipumps. Reference: Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart. Parlakian A, Charvet C, Escoubet B, Mericskay M, Molkentin JD, Gary-Bobo G, De Windt LJ, Ludosky MA, Paulin D, Daegelen D, Tuil D, Li Z. Circulation. 2005 Nov 8;112(19):2930-9. PMID: 16260633
2017-12-21 | GSE84142 | GEO
Project description:Ablation of the Srf gene in dopaminoceptive neurons of the brain was performed using the Cre/loxP system, with the recombinase expressed from a BAC-derived Drd1a promoter. Our goal was to analyze how loss of SRF will affect acitivity-regulated transcription induced by strong stimulation, i.e. cocaine. Keywords: Treatment x Genotype Animals were injected i.p. with either 25 mg/kg cocaine or saline and sacrificed after one hour by cervical dislocation. Expression profiling was performed using total RNA isolated from the striatum.
2010-03-04 | E-GEOD-10870 | biostudies-arrayexpress
Project description:To identify genes regulated by SRF in response to increased neuronal activity whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of kainic acid-induced genes were performed. We found that loss of SRF in DG leads to specific deficits in activity-induced gene expression. Identified genes functions are associated with synapse plasticity, epilepsy, outgrowth of neurites, behavior and MAPK signaling pathway. The microarray experiment was performed to identify SRF-dependent activity-induced genes, using brain-specific, inducible SRF gene knockout mice. Conditional mutants of Srf were obtained by crossing mice in which Srf gene was flanked by loxP sites (Srf f/f) with an CaMKCreERT2 line to ablate its expression exclusively in excitatory forebrain neurons. Knockouts (KO = Srf f/f;CaMKCreERT2) and control littermates (CTR = Srf f/f) were used in the experiments. To enable time-specific induction of SRF deletion, adult mice, were injected with tamoxifen. Global gene expression induced by kainic acid (KA, 35-50 mg/kg) was analyzed. At 6 hours after seizures induction (seizures severity 5; according to modified Racine scale) or saline injection, CTR and KO animals were sacrificed and dentate gyrus was microdissected and used for RNA isolation. In order to identify SRF-regulated genes, we used Illumina MouseWG-6 v2.0 Expression BeadChips.
2015-02-02 | E-GEOD-60772 | biostudies-arrayexpress
Project description:this dataset encompasses the cardiac transcriptomic changes elicited in myocardial tissues of 4months-old mice at 4 hours after a single ZT0 prednisone (1mg/kg i.p.) injection, or vehicle, in cardiomyocyte-KLF15-WT versus cardiomyocyte-KLF15-KO conditions (inducible, tamoxifen-driven ablation right prior to drug pulse).
2024-01-13 | GSE252857 | GEO
Project description:this dataset encompasses the cardiac transcriptomic changes elicited in myocardial tissues of 4months-old male mice at 4 hours after a single ZT0 prednisone (1mg/kg i.p.) injection, or vehicle, in cardiomyocyte-GR-WT versus cardiomyocyte-GR-KO conditions (inducible, tamoxifen-driven ablation right prior to drug pulse).
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Project description:Serum response factor (SRF) is a transcription factor that binds to the serum response element (SRE) of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice were smaller and had lower blood glucose and triglyceride levels compared with control mice. Srf-deficient livers were also smaller than control livers, hepatocyte morphology was abnormal, and liver-cell proliferation and viability was compromised. Gene array and quantitative RT-PCR analysis of SRF depleted livers revealed a reduction in mRNAs encoding components of the growth hormone/IGF1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes. Conclusion: SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression. Experiment Overall Design: Total RNA was harvested from the following sources and used for Affymetrix array analysis following manufacturer defined protocols: Experiment Overall Design: control liver (Srf loxP/+ AlfpCre): 3 male mice (3 weeks old) Experiment Overall Design: mutant liver (Srf loxP/loxP AlfpCre): 3 male mice (3 weeks old), tissue used lacked Srf
2009-03-07 | E-GEOD-13333 | biostudies-arrayexpress
Project description:Previous efforts to conditionally delete the Srf transcription factor in smooth muscle lineages were met with early demise of the mouse due to a gastrointestinal (GI) obstruction phenotype. We have developed a new, more VSMC selective Cre recombinase mouse (Itga8-CreERT2), that circumvents the GI phenotype thus affording the opportunity to evaluate, in an unambiguous manner, VSMC phenotypes where Srf is reduced. The mice live for at least 6 months post-tamoxifen and here we report the first RNA-seq experiments in mouse aortic SMC where Srf is reduced.
2020-04-18 | GSE138824 | GEO
Project description:To identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this “cardiac aging” model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function. The generation and characterization of transgenic mice with mild cardiac-specific overexpression of SRF was previously reported (Zhang et al., 2003). At 6 months of age, the transgenic mice manifested cardiac changes suggestive of an “aged heart” (Zhang et al., 2003). Therefore, 6-month-old transgenic and non-transgenic mice were used in this study. Cardiac gene expression in SRF Tg heart was compared to that of wild-type mice.
2011-08-02 | E-GEOD-19874 | biostudies-arrayexpress
Project description:The overall objective of the project is to evaluate the effects of loss of function of iron regulatory proteins (IRP1, encoded by Aco1)-1 and -2 (IRP2, encoded by Ireb2) during adult life. Mice carrying floxed Aco1 and Ireb2 alleles were crossed to a knockin strain expressing a tamoxifen-inducible CRE recombinase under the control of the Rosa26 promoter. The resulting Aco1flox/flox,Ireb2flox/flox,Rosa26+/CreERT2 mice are designated P1/2-KO; littermates lacking the CreER sequence (Aco1flox/flox,Ireb2flox/flox,Rosa26+/+) serve as reference and are designated P1/2-CTR. Adult mice were injected (i.p.) with tamoxifen on day 1 and day 3 to ablate the IRPs in the whole body, and were sacrificed on day 10 for analysis. Bone marrow cells were collected and LY6G+ cells were magnetically sorted for proteome analysis by LC-MS/MS using an Ultimate 3000 UPLC system connected to an Orbitrap Exploris 480 mass spectrometer.
2023-03-11 | PXD032077 | Pride
Project description:To identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this “cardiac aging” model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function. The generation and characterization of transgenic mice with mild cardiac-specific overexpression of SRF was previously reported (Zhang et al., 2003). At 6 months of age, the transgenic mice manifested cardiac changes suggestive of an “aged heart” (Zhang et al., 2003). Therefore, 6-month-old transgenic and non-transgenic mice were used in this study.
2011-08-03 | GSE19874 | GEO