Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA395354 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5858230.fastq.gz | Fastqsanger.gz | |||
| SRR5858231.fastq.gz | Fastqsanger.gz | |||
| SRR5858232.fastq.gz | Fastqsanger.gz | |||
| SRR5858233.fastq.gz | Fastqsanger.gz | |||
| SRR5858234.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
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Project description:FTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories. Microarrays were used to survey the effect of FTY720 treatment during contextual fear conditioning on hippocampal gene expression. Total RNA was isolated from individual hippocampi of SCID mice 1 hour following fear consolidation testing after the third day of FTY720 or saline treatment. Eight arrays were run in total: 4 FTY720-treated mice and 4 saline-treated control mice.
2014-05-12 | E-GEOD-57015 | biostudies-arrayexpress
Project description:Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis
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Project description:The clinical outcomes of M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) are poor. Here we report that FTY720 (Fingolimod), a sphingosine analogue and an FDA approved drug for treatment of multiple sclerosis, showed great antitumorigenic activity against Kasumi-1 cell line, xenograft mouse model and leukemic blasts isolated from AML-M2 with t(8;21) patients. Primary investigation indicated that FTY720 caused cell apoptosis through caspase and protein phosphatase 2A (PP2A) activation. Transcriptomic profiling further revealed that FTY720 treatment could upregulate AML1 target genes and interfere with genes involved in ceramide synthesis. FTY720 treatment led to the elimination of AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720 treatment resulted in rapid and significant increment of pro-apoptotic ceramide levels, determined by HPLC-ESI-MS/MS (high-performance liquid chromatography-electrospray ionization tandem mass spectrometry) based lipidomic approaches. Additionally, structural simulation model indicated that the directly binding of ceramide to inhibitor 2 of PP2A (I2PP2A) could reactivate PP2A and cause cell death. This study demonstrates, for the first time, that accumulation of ceramide plays a central role in FTY720 induced cell death of AML-M2 with t(8;21). Targeting sphingolipid metabolism by using FTY720 may provide novel insight into drug development for AML-M2 treatment. A six chip study using total RNA recovered from three separate cultures of DMSO-treated Kasumi-1 cells and three separate cultures of FTY720-treated Kasumi-1 cells.Each chip measures the expression level of genes from DMSO-/FTY720-treated Kasumi-1 cells.
2014-04-30 | E-GEOD-55772 | biostudies-arrayexpress
Project description:MP4-induced experimental autoimmune encephalomyelitis (EAE) is a B cell-dependent mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and central nervous system (CNS) itself.
2020-02-07 | GSE94636 | GEO
Project description:FTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories. Microarrays were used to survey the effect of FTY720 treatment during contextual fear conditioning on hippocampal gene expression.
2014-05-12 | GSE57015 | GEO
Project description:The clinical outcomes of M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) are poor. Here we report that FTY720 (Fingolimod), a sphingosine analogue and an FDA approved drug for treatment of multiple sclerosis, showed great antitumorigenic activity against Kasumi-1 cell line, xenograft mouse model and leukemic blasts isolated from AML-M2 with t(8;21) patients. Primary investigation indicated that FTY720 caused cell apoptosis through caspase and protein phosphatase 2A (PP2A) activation. Transcriptomic profiling further revealed that FTY720 treatment could upregulate AML1 target genes and interfere with genes involved in ceramide synthesis. FTY720 treatment led to the elimination of AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720 treatment resulted in rapid and significant increment of pro-apoptotic ceramide levels, determined by HPLC-ESI-MS/MS (high-performance liquid chromatography-electrospray ionization tandem mass spectrometry) based lipidomic approaches. Additionally, structural simulation model indicated that the directly binding of ceramide to inhibitor 2 of PP2A (I2PP2A) could reactivate PP2A and cause cell death. This study demonstrates, for the first time, that accumulation of ceramide plays a central role in FTY720 induced cell death of AML-M2 with t(8;21). Targeting sphingolipid metabolism by using FTY720 may provide novel insight into drug development for AML-M2 treatment.
2014-04-30 | GSE55772 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:A synthetic analog of sphingosine named FTY720 (Fingolimod), phosphorylated by sphingosine kinase-2, interacts with sphingosine-1-phosphate (S1P) receptors expressed on various cells. FTY720 suppresses the disease activity of multiple sclerosis (MS) chiefly by inhibiting S1P-dependent egress of autoreactive T lymphocytes from secondary lymphoid organs, and possibly by exerting anti-inflammmatory and neuroprotective effects directly on brain cells. However, at present, biological effects of FTY720 on human microglia are largely unknown. We studied FTY720-mediated apoptosis of a human microglia cell line HMO6. The exposure of HMO6 cells to non-phosphorylated FTY720 (FTY720-non-P) induced apoptosis in a dose-dependent manner with IC50 of 10.6±2.0 microM, accompanied by the cleavage of caspase-7 and caspase-3 but not of caspase-9. The apoptosis was inhibited by Z-DQMD-FMK, a caspase-3 inhibitor, but not by Pertussis toxin, a Gi protein inhibitor, suramin, a S1P3/S1P5 inhibitor, or W123, a S1P1 competitive antagonist, although HMO6 expressed S1P1, S1P2, and S1P3. Furthermore, both phosphorylated FTY720 (FTY720-P) and SEW2871, a S1P1 selective agonist did not induce apoptosis of HMO6. Genome-wide gene expression profiling and molecular network analysis indicated activation of transcriptional regulation by sterol regulatory element-binding protein (SREBP) in FTY720-non-P-treated HMO6 cells. Western blot verified activation of SREBP2 in these cells, and apoptosis was enhanced by pretreatment with simvastatin, an activator of SREBP2, and by overexpression of the N-terminal fragment of SREBP2. These observations suggest that FTY720-non-P-induced apoptosis of HMO6 human microglia is independent of S1P receptor binding, and positively regulated by the SREBP2-dependent proapoptotic signaling pathway. The HMO6 cell line was established by immortalizing cultured microglia isolated from human embryonic telencephalon tissues with a retroviral vector PASK1.2 encoding v-myc oncogene (Nagai et al. Neurobiol. Dis. 8: 1057-1068, 2001). HMO6 cells express the markers of the microglia/macrophage lineage cells, including CD11b, CD68, CD86, HLA-ABC, HLA-DR, and ricinus communis agglutinin lectin-1 (RCA), serving as a model of human microglia both in vitro and in vivo. The cells were exposed for 2 hours to 10 microM FTY720-non-P dissolved in dimethyl sulfoxide (DMSO) or ethanol or exposed to the vehicle.
2011-04-16 | E-GEOD-28642 | biostudies-arrayexpress
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff3 knock-out mouse model, 21 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
2010-09-20 | GSE23819 | GEO