Dysregulated genes in connexin 30 deficient mice microglia
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PROVIDER: PRJNA448527 | ENA |
REPOSITORIES: ENA
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Project description:Dysregulated genes in connexin 30 deficient mice microglia [EAE]
| PRJNA448529 | ENA
Project description:Dysregulated genes in connexin 30 deficient mice microglia [naive]
| PRJNA448530 | ENA
Project description:Objective: Connexins are known to compose gap junctions by a pair of hemichannels connected in a head to head configuration. Each hemichannel is composed by hexameric cluster of connexins. There are 20 members of connexins known as connexin family in mice, and are expressed on each cell surface in different fashion. Connexin 30 (Cx30) is mainly expressed on the surface of oligodendroglia and astrocyte in central nervous system (CNS), but little is known about the functional relevance in neuroinflammatory diseases. To elucidate the role of Cx30 in the pathogenesis of neuroinflammatory disease, we induced experimental autoimmune encephalomyelitis (EAE) on Cx30 knock-out (Cx30-KO) mice and analyzed the clinical and neuropathological findings with wild-type control. Methods: C57BL/6J and Cx30-KO mice > 12 weeks of age were used in this study (N > 3 in each group). EAE was induced by immunization of mice with MOG35-55 peptide emulsified in CFA at a dose of 200 μg per mouse, followed by the administration of pertussis toxin (500 ng per mouse) on days 0 and 2. Mice were sacrificed and brain, spinal cord, spleen, and optic nerve were harvested for immunohistochemical analyses at the acute and chronic phases of EAE. Mice with EAE were scored as follows: 0, no disease; 1, limp tail; 2, abnormal gait and hind limb weakness (shaking); 2.5, paralysis of one hind limb; 3, paralysis of two hind limb; 3.5, ascending paralysis (able to move around); 4, tetraplegia; and 5, moribund (death). At the onset and chronic stage of EAE, mononuclear cells were isolated and analyzed by flow cytometry to check the distinct characteristics of cellular populations in inflamed CNS lesions. Results: Initial screening of immunohistological difference revealed basic activation of microglial cells in naïve Cx30-KO mice without any behavioral phenotype. Clinical signs of EAE were ameliorated in the Cx30-KO mice than in the control group mainly during the chronic phase of disease course. Immunohistochemical analyses of the fourth lumbar segment, brain and optic nerve revealed increased number of microglia in the Cx30-KO mice. Flow cytometric analysis also confirmed the findings. In contrast, there were no significant change in astroglial or oligodendroglial phenotype. Conclusion: Microglial activation appears to be the key factor in the Cx30-KO mice EAE with alleviation of chronic disease scores. Unexpectedly, microglia were already activated in naïve CNS, indicating protective phenotypic change of microglia in Cx30-KO mice.
2018-04-04 | GSE112619 | GEO
Project description:Objective: Connexins are known to compose gap junctions by a pair of hemichannels connected in a head to head configuration. Each hemichannel is composed by hexameric cluster of connexins. There are 20 members of connexins known as connexin family in mice, and are expressed on each cell surface in different fashion. Connexin 30 (Cx30) is mainly expressed on the surface of oligodendroglia and astrocyte in central nervous system (CNS), but little is known about the functional relevance in neuroinflammatory diseases. To elucidate the role of Cx30 in the pathogenesis of neuroinflammatory disease, we induced experimental autoimmune encephalomyelitis (EAE) on Cx30 knock-out (Cx30-KO) mice and analyzed the clinical and neuropathological findings with wild-type control. Methods: C57BL/6J and Cx30-KO mice > 12 weeks of age were used in this study (N > 3 in each group). EAE was induced by immunization of mice with MOG35-55 peptide emulsified in CFA at a dose of 200 μg per mouse, followed by the administration of pertussis toxin (500 ng per mouse) on days 0 and 2. Mice were sacrificed and brain, spinal cord, spleen, and optic nerve were harvested for immunohistochemical analyses at the acute and chronic phases of EAE. Mice with EAE were scored as follows: 0, no disease; 1, limp tail; 2, abnormal gait and hind limb weakness (shaking); 2.5, paralysis of one hind limb; 3, paralysis of two hind limb; 3.5, ascending paralysis (able to move around); 4, tetraplegia; and 5, moribund (death). At the onset and chronic stage of EAE, mononuclear cells were isolated and analyzed by flow cytometry to check the distinct characteristics of cellular populations in inflamed CNS lesions. Results: Initial screening of immunohistological difference revealed basic activation of microglial cells in naïve Cx30-KO mice without any behavioral phenotype. Clinical signs of EAE were ameliorated in the Cx30-KO mice than in the control group mainly during the chronic phase of disease course. Immunohistochemical analyses of the fourth lumbar segment, brain and optic nerve revealed increased number of microglia in the Cx30-KO mice. Flow cytometric analysis also confirmed the findings. In contrast, there were no significant change in astroglial or oligodendroglial phenotype. Conclusion: Microglial activation appears to be the key factor in the Cx30-KO mice EAE with alleviation of chronic disease scores. Unexpectedly, microglia were already activated in naïve CNS, indicating protective phenotypic change of microglia in Cx30-KO mice.
2018-04-04 | GSE112620 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-04 | GSE112621 | GEO
Project description:Effect of the ablation of connexin 30 in the stria vascularis
2007-04-16 | E-MEXP-558 | biostudies-arrayexpress
Project description:Transcription is dysregulated in Polη-deficient cells
| PRJNA685542 | ENA
Project description:CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-Seq. In 2 mos mice, Cx3cr1 deletion resulted in the downregulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a compatible fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.
2019-10-01 | GSE130960 | GEO
Project description:CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA sequencing (RNA-Seq). In 2 mos mice, Cx3cr1 deletion resulted in the downregulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature.
2019-11-25 | GSE131869 | GEO
Project description:Loss-of-function mutations in CLN3 cause juvenile Batten disease, featuring neurodegeneration and early-stage neuroinflammation. How loss of CLN3 function leads to early neuroinflammation is not yet understood. Here, we have comprehensively studied microglia from Cln3∆ex7/8 mice, a genetically accurate disease model. Loss of CLN3 function in microglia leads to lysosomal storage material accumulation and abnormal morphology of subcellular organelles. We also discovered pathological proteomic signatures consistent with defects in lysosomal function and indicative of abnormal lipid metabolism. CLN3-deficient microglia were unable to efficiently turnover myelin and metabolize the associated lipids, showing defects in lipid droplet formation and cholesterol accumulation.
2024-10-23 | PXD048550 | Pride