Expression data from the mouse liver with constitutively active FoxO3
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE44977 | GEO | 2019/02/22
REPOSITORIES: GEO
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Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice. Trangenic vs non-transgenic mice onto Foxo3+/- vs Foxo3-/- genotype
2013-06-08 | E-GEOD-45389 | biostudies-arrayexpress
Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice.
2013-06-08 | GSE45389 | GEO
Project description:We have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis.
2012-09-13 | GSE21089 | GEO
Project description:We have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis. We sought to determine the transcriptional differences in forebrains from E12.5 mice expressing a constitutively active alleleof FoxO3 under the control of the forebrain-specific CaMKIIa promoter. To this end two time-pregnant dams were sacrificed 12 days after the vaginal plug was detected, and the embryos were prepared. Visual staging of the embryos confirmed their age. Genotyping and luciferase measurements were performed in order to assess presence and acitivity of the transgenes.
2012-09-13 | E-GEOD-21089 | biostudies-arrayexpress
Project description:During female reproductive life, ovarian follicle reserve is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. Here we show that overexpression of constitutively active FOXO3 can increase ovarian reproductive capacity in mice. We find increased follicle numbers and decreased gonadotropin levels in aging FOXO3-transgenic mice compared with wild-type littermates, suggesting maintenance of a greater ovarian reserve. Based on cumulative progeny in aging animals, we find 31-49% increased fertility in transgenic females. The gene expression profile of Foxo3-/- knockout ovaries appears older than that of wild-type littermates, and the transgene induces a younger-looking profile, restoring much of the wild-type transcriptome. This is the first gain-of-function model of augmented reproductive reserve in mice, thus emphasizing the role of Foxo3 as a guardian of the ovarian follicle pool in mammals and a potential determinant of the onset of menopause.
| S-EPMC4504230 | biostudies-literature
Project description:Activation of hepatic NF-kB signaling induces inflammation and ultimately fibrosis. To investigate the underlying mechanism, we used microarrays to detail the global programme of gene expression which is regulated by hepatic NF-kB signaling.
2012-04-01 | GSE28085 | GEO
Project description:Activation of hepatic NF-kB signaling induces inflammation and ultimately fibrosis. To investigate the underlying mechanism, we used microarrays to detail the global programme of gene expression which is regulated by hepatic NF-kB signaling. We generated transgenic mice which express a constitutively active IKK2 controlled under the LAP promotor. The liver samples were collected from transgenic mice as well as from control animals at the age of 4 weeks. RNA extraction was performed from these liver samples and hybridized on Affymetrix microarrays.
2012-03-31 | E-GEOD-28085 | biostudies-arrayexpress
Project description:Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter results in disulfide formation between protein (hetero)dimers that alter protein function until the cellular redox has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the FOXO4 transcription factor. Here, we present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptor IPO7 forms a disulfide-dependent heterodimer with FOXO3, but not with FOXO4, which is required for reactive oxygen species (ROS)-induced nuclear translocation . These findings suggest that evolutionary acquisition of cysteines has contributed to functional divergence of FOXO paralogs.
2014-08-26 | PXD001018 | Pride
Project description:Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter results in disulfide formation between protein (hetero)dimers that alter protein function until the cellular redox has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the FOXO4 transcription factor. Here, we present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptor IPO7 forms a disulfide-dependent heterodimer with FOXO3, but not with FOXO4, which is required for reactive oxygen species (ROS)-induced nuclear translocation . These findings suggest that evolutionary acquisition of cysteines has contributed to functional divergence of FOXO paralogs.
2014-08-26 | PXD001040 | Pride