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Differential expression analyses in microglial cells from APP-Psen1/+;Cx3cr1-Cre::ERT2/+; Vhl Flox/– mice treated with tamoxifen vs APP-Psen1/+;Cx3cr1-Cre::ERT2/+; Vhl Flox/– mice non treated

ABSTRACT: Microglial cells were isolated by flow citometry using specific markers (CD45+/ CD11b+) and their global gene expression profile was analyzed. This data were used to study the role of HIF1A in microglia associated to Aβ plaques. In this dataset, we include the expression data obtained in microglial cells from a model of gain of function of HIF1A in APP-PSEN1/+ mice. (18 moth-old-age) mice model using a specific marker for this cell type (CD31+). Functional enrichment analyses were carried out through GSEA, where we have included specific categories potentially involved with blood vessel formation.

ORGANISM(S): Mus musculus

PROVIDER: GSE168059 | GEO | 2021/03/08

REPOSITORIES: GEO

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Differential expression analyses in microglial cells from APP-Psen1/+ Cx3cr1-Cre::ERT2/+ Vhl Flox/– mice treated with tamoxifen vs APP-Psen1/+ Cx3cr1-Cre::ERT2/+ Vhl Flox/– mice non treated

Project description:Differential expression analyses in microglial cells from APP-Psen1/+ Cx3cr1-Cre::ERT2/+ Vhl Flox/– mice treated with tamoxifen vs APP-Psen1/+ Cx3cr1-Cre::ERT2/+ Vhl Flox/– mice non treated

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Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes.

Project description:Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology, function and disease. While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts, few target osteocytes specifically, particularly mature osteocytes. Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5' and 3' regions of the Sost gene (Sost ERT2 Cre). Four founder lines were crossed with the Ai9 Cre reporter mice. One founder line showed high and specific activity in mature osteocytes. Bones and organs were imaged and fluorescent signal quantitated. While no activity was observed in 2 day old pups, by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or 'leaky' with age. The percentage of positive osteocytes increased following tamoxifen injection, especially in males, with 43% to 95% positive cells compared to 19% to 32% in females. No signal was observed in any bone surface cell, bone marrow, nor in muscle with or without tamoxifen injection. No spontaneous signal was observed in any other organ. However, with tamoxifen injection, a few positive cells were observed in kidney, eye, lung, heart and brain. All other organs, 28 in total, were negative with tamoxifen injection. However, with age, a muscle phenotype was apparent in the Sost-ERT2 Cre mice. Therefore, although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes, the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.

| S-EPMC6382861 | biostudies-literature

Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice.

Project description:There is an increasing trend in studies utilizing cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limitations such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (Gnrh)-driven CRE-expressing mice both target GnRH neurons. However, a direct comparison of the cells targeted and their phenotypic outcome have not yet been presented. To compare where recombination takes place, we crossed the Gnrh-cre and Lhrh-cre lines with the Rosa26-LacZ reporter mouse. Lhrh-cre allowed recombination of the Rosa26-LacZ gene in ∼700 cells, which is comparable to the GnRH neuronal population. Surprisingly, there were > 20 times more LacZ expressing cells in the adult Gnrh-cre:Rosa26-LacZ than the Lhrh-cre:Rosa26-LacZ brain. The greatest differences in targeting of the Gnrh-cre and Lhrh-cre lines were found in the septum, the suprachiasmatic nucleus, and the septohypothalamic area. This difference in cells targeted was present from embryonic day 12. A prior study using the Gnrh-cre to delete the transcription factor Otx2 found fewer GnRH neurons, leading to male and female subfertility. To recapitulate this study, we performed a fertility assay in Otx2:Lhrh-cre mice. We confirmed the requirement for Otx2 in GnRH neuron development, fertility and correct gonadotropin hormone release in Otx2:Lhrh-cre males, but the subfertility was more modest than in Otx2:Gnrh-cre and absent in female Otx2:Lhrh-cre. This suggests that ectopic expression of Gnrh-cre contributes to the reproductive phenotype observed. Finally, the Cre alleles caused germline recombination of the flox allele when transmitted from either parent, generating embryonic lethal knock-out offspring, producing smaller live litters.

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The acceleration of reproductive aging in Nrg1flox/flox ;Cyp19-Cre female mice.

Project description:Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop a new strategy for improving fertility in older women prior to menopause. In the ovary of 6-month-old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor-positive endocrine cells and (ii) actin-rich fibrotic cells expressing collagen. Both the endocrine and fibrotic cells disappeared following long-term treatment with a GnRH antagonist, indicating that the high levels of serum LH induced the survival of both cell types and the abnormal endocrine profile to reduce fertility. Moreover, follicular development to the antral stages was observed with reduced LH and the disappearance of the abnormal stromal cells. Mice treated with the GnRH antagonist regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months. We conclude that endocrine and matrix alternations occur within the ovarian stroma with increasing age and that abolishing these alternations resets the cyclical release of LH. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause.

| S-EPMC5676068 | biostudies-other

The quantitative analysis of transcriptomes derived from MLL-AF10 flox cells and MLL-AF10 (Tip60 flox/flox, Cre-ERT2) cells with or without the treatment of 4-OHT

Project description:Chromosome translocations involving the MLL gene are common rearrangements in leukemia. Such translocations fuse the MLL 5’-region in frame to partner genes , and the resultant fusion proteins can cause MLL-related leukemia. MLL-fusions activate transcription of target genes such as the HoxA cluster and Meis1, but the underlying mechanisms remain elusive. We found that the MLL-AF10 fusion recruits Tip60 to the Hoxa9 locus, where it acetylates H2A.Z, thereby promoting Hoxa9 expression. Following conditional deletion of Tip60, hypoacetylation of H2A.Z was accompanied by recruitment of Ezh2, the catalytic subunit of PRC2, suggesting that nucleosomes with hypoacetylated H2A.Z are the preferential targets of Ezh2. Our findings suggest that MLL-AF10 achieves active chromatin states by recruiting Tip60, which acetylates H2A.Z to prevent gene silencing by Ezh2.

2021-06-30 | GSE142558 | GEO

Adiponectin-cre FTO flox/flox and FTO flox/flox mouse white fat tissues

Project description:Single nucleotide polymorphisms in intron 1 of the fat mass and obesity-associated (FTO) gene were found to be associated with an increased risk of adult obesity. Enhanced FTO expression in mice leads to hyperphagia, increased fat mass, and higher body weight. Neuronal-specific FTOâ??deleted mice have an identical lean body weight phenotype to global FTO-deleted mice. The physiological role of adipose FTO in the homeostasis of energy regulation remains to be elucidated. We used microarrays to elucidate the metabolic pathways that are regulated by FTO in the white fat. FTO flox/flox and Adiponectin-cre FTO flox/flox (AFO) mice were fed with chow diet. White fat tissues from epididymal adipose pad were harvested under ad lib condition for RNA isolation. Three independent pools of FTO flox/flox and AFO mouse white fat RNA were included in the study.

2016-07-03 | E-GEOD-65098 | biostudies-arrayexpress

The genome-wide maps of H3K27me3 in MLL-AF10 (Tip60 flox/flox, Cre-ERT2) cells (MATIP cells) with or without the treatment of 4-OHT

2021-06-30 | GSE142557 | GEO

Gene expression profile of Dnmt1 flox/flox, Dnmt3a flox/flox, Dnmt3b flox/flox, cre negative (Wild type) and Dnmt1 flox/flox, Dnmt3a flox/flox, Dnmt3b flox/flox, Rx-cre (Triple mutant) murine retina transcriptomes

Project description:Purpose: The goal of this study was to identify the gene expression profile of mouse retina which carries deletions in Dnmt1, Dnmt3a and Dnmt3b genes. Method: Retinal mRNA profiles of Postnatal day 15 wild type mice and Dnmt1, Dnmt3a and Dnmt3b mutant mice were generated by deep-sequencing

2016-11-28 | GSE81191 | GEO

Next Generation Sequencing analysis of Hes1+/+ Cre-ERT2 and Hes1fl/fl Cre-ERT2 bone marrow derived macrophages transcriptomes.

Project description:To evaluate the potential role of Hes1 in regulation of type I IFNs and the downstream ISGs expression, we generated the bone marrow-derived macrophages (BMDMs) from Hes1+/+ Cre-ERT2 and Hes1fl/fl Cre-ERT2 mice. RNA-sequencing analysis of Poly(I:C) [(polyinosinic: polycytidylic acid), a mimic of viral double-stranded RNA]-treated BMDMs revealed that 49 genes were induced more than two-fold by Poly(I:C) for 3 hrs in Hes1-deficient BMDMs relative to their expression in Hes1+/+Cre-ERT2 cells. Notably, 67.3% of these upregulated genes were ISGs by screening the Interferome database, suggesting that Hes1 inhibits expression of TLR-mediated ISGs,these results indicated that Hes1 negatively regulates TLR3-mediated induction of ISGs in macrophages.

2019-04-16 | GSE111169 | GEO

Gene expression of microglia from wild type, Gba flox/flox; Nestin-Cre, and Gba flox/flox; Nestin-Cre; Mincle-/- mice

Project description:To investigate the contribution of Mincle in neuronopathic Gaucher disease, we established Gba flox/flox; Nestin-Cre mice and crossed them with Mincle deficient mice. RNA sequencing of microglia from these mice revealed Axl, a phaogocytic receptor was upregulated in Gba flox/flox; Nestin-Cre mice. In addition, Tnf was upregulated in Gba flox/flox; Nestin-Cre mice in a Mincle-dependent manner. Our further study elucidated that Mincle, Axl and TNF are involved in the pathology of Gaucher disease.

2023-02-03 | GSE202711 | GEO

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