Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB19577 | ENA |
REPOSITORIES: ENA
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Project description:Microglia, the resident macrophages in the central nervous system (CNS), have been intensively studied using rodent genetic models, including the Cx3cr1-Cre mouse line. These mice have enabled the in-depth analyses of the biological features and functions of myeloid cells, including microglia. Occasionally, these Cx3cr1CreERT2 tools have yielded conflicting outcomes, the underlying mechanism of which remains unclear. Here, we comparatively characterize the two available Cx3cr1CreERT2 lines (Cx3cr1CreERT2(Litt) and Cx3cr1CreERT2(Jung)). We find a mouse line-specific and TAM-dependent persistent induction of CDKN1A in microglia of Cx3cr1CreERT2(Litt) mice, but not in those of Cx3cr1CreERT2(Jung) mice, which affects experimental readouts with altered proliferative capacity. Furthermore, aberrant cellular alterations observed in postnatal Cx3cr1CreERT2(Litt) microglia are mitigated by a functional inhibition of CDKN1A. Together, these findings underscore the significance of mouse line-specific phenomena that alter microglial outcomes in a CDKN1A-dependent manner, highlighting the importance of rigorous validation of genetic mouse tools.
2025-08-06 | GSE304770 | GEO
Project description:The EZH2 histone methyltransferase is required for B cells to form germinal centers (GCs). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21Cip1). Deletion of Cdkn1a rescued the GC reaction in Ezh2 knockout mice. To study the effects of EZH2 in primary GC B cells we generated and validated a 3D B cell follicular organoid system that mimics the endogenous GC reaction. Using this system we found that depletion of EZH2 suppressed G1 to S phase transition of GC B cells in a Cdkn1a dependent manner. GC B cells of Cdkn1a;Ezh2 double knockout mice exhibited high levels of phospho Rb, indicating that loss of Cdkn1a allows progression of cell cycle. Moreover, we show that the transcription factor E2F1 plays a major role in inducing EZH2 upregulation during the GC reaction. E2F1 deficient mice manifest impaired GC responses, which was rescued by restoring EZH2 expression, thus defining a positive feedback loop whereby EZH2 controls GC B cell proliferation by suppressing CDKN1A, allowing cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1.
2017-08-10 | GSE95491 | GEO
Project description:The Cx3cr1CreERT2(Litt) mouse model is widely used for in-depth studies of myeloid cells, including microglia. In this study, we employed single-cell RNA sequencing (scRNA-seq) to characterize microglial responses to tamoxifen (TAM) administration in adult Cx3cr1CreERT2(Litt) mice. Our analysis revealed a prolonged TAM-dependent induction of CDKN1A in the microglial population, highlighting a effect of the Cre-induction system itself.
2025-08-15 | GSE304771 | GEO
Project description:We previously discovered a sex-by-genotype defect in microglia function using a germline heterozygous knockout mouse model of Neurofibromatosis type 1 (Nf1+/- mice), in which only microglia from male Nf1+/- mice exhibited defects in purinergic signaling. Herein, we leveraged an unbiased proteomic approach to demonstrate that male, but not female, heterozygous Nf1+/- microglia exhibit differences in protein expression, which largely reflect pathways involved cytoskeletal organization. In keeping with potential defects in cytoskeletal function, only male Nf1+/- microglia had reduced process arborization and surveillance capacity. Next, to determine whether these microglial defects were cell autonomous or reflected adaptive responses to Nf1 heterozygosity in other cells in the brain, we generated conditional microglia Nf1-mutant knockout mice by intercrossing Nf1flox/flox with Cx3cr1-CreER mice (Nf1flox/wt; Cx3cr1-CreER mice, Nf1MG+/- mice). Surprisingly, neither male nor female Nf1MG+/- mouse microglia had impaired process arborization or surveillance capacity. In contrast, when Nf1 heterozygosity was generated in neurons, astrocytes and oligodendrocytes by intercrossing Nf1flox/flox with hGFAP-Cre mice (Nf1flox/wt; hGFAP-Cre mice, Nf1GFAP+/- mice), the microglia defects found in Nf1+/- mice were recapitulated. Collectively, these data reveal that Nf1+/- sexually dimorphic microglia abnormalities are likely not cell-intrinsic properties, but rather reflect a response to Nf1 heterozygosity in other brain cells.
2023-05-10 | PXD035881 | Pride
Project description:Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+ CD4+ T cells during Type 2 inflammation in helminth infections. Here, we used a fate-mapping mouse model to characterize CX3CR1+ CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni helminth infections, revealing CX3CR1+ CD4+ T cells to be an activated tissue homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA-sequencing analysis of fate-mapped CX3CR1+ CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+ TCF-1+ PD1+ CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells result in fewer CX3CR1+ CD4+ during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+ CD4+ T cells during Type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance
2023-08-12 | GSE239846 | GEO
Project description:Microglia RNAseq from ARID1A fl/fl cx3cr1-cre mouse line Raw sequence reads
| PRJNA811756 | ENA
Project description:Angiotensin Converting Enzyme (ACE) has been studied for its role in the regulation of myeloid cell bactericidal and antitumor activity. Here, we generated a mouse model with Tamoxifen-dependent ACE expression with Cx3CR1-Cre control. These mice were crossed to 5xFAD and 9 month forebrains were harvested for their nuclei to assess the ACE-dependent changes in amyloid-reactive microglia.
2025-03-24 | GSE288410 | GEO
Project description:Angiotensin Converting Enzyme (ACE) has been studied for its role in the regulation of myeloid cell bactericidal and antitumor activity. Here, we generated a mouse model with Tamoxifen-dependent ACE expression and Cx3CR1-Cre control. These mice were crossed to 5xFAD and 9 month forebrains were harvested and FFPE processed to assess the ACE-dependent changes in amyloid-reactive microglia.
2025-03-24 | GSE288280 | GEO
Project description:Secondary injury causes death and dependence after spontaneous intracerebral haemorrhage (ICH). Having found that ICH is associated with activation of genes regulated by the transcription factor Nrf2, particularly in mononuclear myeloid cells (for example, monocyte-derived cells (MdC) and microglia), we sought to determine the importance of Nrf2 to mononuclear myeloid cell responses and their impact on ICH pathology. We used intrastriatal injection of collagenase to induce ICH in both wild-type mice, and knockout mice with Cx3cr1-Cre-mediated excision of Nrf2 (Nfe2l2) exon 5.
2024-08-13 | E-MTAB-14324 | biostudies-arrayexpress
Project description:Cx3cr1CreER driven Cre-recombinase (Cre) is a widely used genetic tool for enabling gene manipulation in microglia and macrophages. However, an in-depth analysis for the possible detrimental effects of Cre-activity in microglia, surprisingly remains missing. Here we demonstrate an age-dependent sensitivity of microglia to Cx3cr1-Cre-toxicity, wherein Cre-induction specifically in early postnatal microglia is detrimental for microglial development, proliferation and function. Tamoxifen (TAM) induced Cre-activity leads to microglial activation, type1-interferon (IFN-1) signaling and increased phagocytosis, causing aberrant synaptic pruning during early postnatal period and anxiety behavior in later age. The detrimental effects of Cre-induction are caused due to DNA-damage induced toxicity in microglia, and is limited to the early postnatal period, showing no detrimental effects in adult microglia. Thus, our study reveals the age-dependent vulnerability of microglia to Cre-activity, thereby highlighting age-dependencies of Cre-action, which could be especially applicable in the broader context of environment-responsive cell-types.
2021-12-08 | GSE190207 | GEO