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Gene expression profiles in the hippocampus of the Rp58 hetero-KO and the control wild-type mice in adulthood and old age.

ABSTRACT: The early onset of microglia activation in the Rp58 hetero-KO mice raised the possibility that chronic inflammation in the brain was induced by mutation even in the early life stage. To test this possibility, we examined gene expression profiles in the hippocampus of the Rp58 hetero-KO and the control wild-type mice in adulthood and old age months. Among the genes whose expression level was down-regulated in the aged wild-type mice, 341 genes were down-regulated in the adulthood Rp58 hetero-KO mice when both were compared with the adulthood wild-type mice. Conversely, the expression levels of 103 genes were up-regulated both in the adulthood Rp58 hetero-KO and the aged wild-type mice. In the pathway enrichment analysis, these 103 up-regulated genes included Cxcl10, Oas2, Oas1a, and Oasl2, which are associated with a pathway of immune response interferon gamma action on extracellular matrix and cell differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE207955 | GEO | 2022/07/16

REPOSITORIES: GEO

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Gene expression profiles in the hippocampus of the Rp58 hetero-KO and the control wild-type mice in adulthood and old age.

Project description:Gene expression profiles in the hippocampus of the Rp58 hetero-KO and the control wild-type mice in adulthood and old age.

| PRJNA857734 | ENA

RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex

Project description:Appropriate number of neurons and glial cells is generated from neural stem cells (NSCs) by the regulation of cell cycle exit and subsequent differentiation. Although the regulatory mechanism remains obscure, Id (inhibitor of differentiation) proteins are known to contribute critically to NSC proliferation by controlling cell cycle. Here we report that a transcriptional factor, RP58, negatively regulates all 4 Id genes (Id1-Id4) in developing cerebral cortex. Consistently, Rp58 knockout (KO) mice demonstrated enhanced astrogenesis accompanied with an excess of NSCs. These phenotypes were mimicked by the overexpression of all Id genes in wild-type cortical progenitors. Furthermore, Rp58 KO phenotypes were rescued by the knockdown of all Id genes in mutant cortical progenitors but not by the knockdown of each single Id gene. Finally, we determined p57 as an effector gene of RP58-Id-mediated cell fate control. These findings establish RP58 as a novel key regulator that controls the self-renewal and differentiation of NSCs and restriction of astrogenesis by repressing all Id genes during corticogenesis.

2014-12-08 | GSE34327 | GEO

RNA profiling of skeletal muscle in RP58 knockout mice

Project description:To predict RP58-regulated genes involved in skeletal myogenesis, RNA profiling experiments were performed, comparing RNA derived from skeletal muscle tissue of a RP58+/+ mouse to that from a RP58 knockout (KO) mouse at E18.5. Importantly, well-known dominant-negative inhibitors of muscle differentiation, the Id family of genes (Id1/Id2/Id3), were upregulated in the RP58 KO muscle. On the contrary, a number of muscle differentiation-related genes, such as Ckm, troponin and Myosin, were downregulated in the same sample. These results indicate that the repressor protein RP58 is important for muscle terminal differentiation, possibly suppressing the gene expression of muscle differentiation genes such as the Ids. Keywords: Knockout tissue Skeletal muscles of WT and RP58 KO mice (E18.5 diaphragm) were dissected under a microscope and RNA was extracted using ISOGEN (Nippongene). After EtOH precipitation, RNA was dissolved into DEPC-DW and its concentration was determined. Microarray analysis - cRNA was synthesized. 10 ug of cRNA were hybridized to Affymetrix mouse 430A 2.0 arrays. Signal intensities were calculated using the RMA method. MAPPFinder (www.genmapp.org) was used to integrate expression data with known pathways.

2009-07-31 | E-GEOD-16595 | biostudies-arrayexpress

RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex

2014-12-08 | E-GEOD-34327 | biostudies-arrayexpress

RNA profiling of skeletal muscle in RP58 knockout mice

2009-07-31 | GSE16595 | GEO

QuantSeq analysis in the hippocampus of WT and PHF2 t/g mice

Project description:Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation status are essential for epigenetic regulation of memory consolidation-related genes. Here, we demonstrated that plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during experience and plays an essential role in memory formation. QuantSeq analysis was performed to examine differential gene expression in the hippocampus of WT and PHF2 t/g mice. Transgenic mice were created by injecting the CMV-Flag-PHF2 vector into fertilized eggs from C57BL6 mice. Transgenic lines were established from 9 founders that were identified via PCR-based genotyping. Among the transgenic lines, mice with high PHF2 expressed brains were singled out for breeding. First, selected heterozygote males were bred with heterozygote females which produced homozygote, heterozygote and wild littermates. Since it is difficult to differentiate between hetero and homo mice with genotyping, we separated homo mice from hetero mice by breeding each of hetero and homo mice with wild type mice and confirming the genotypes of their offspring. In other words, hetero mice bred with wild type mice would have both wild type and hetero genotype of offspring, while homo mice bred with wild type mice would only have hetero genotype of offspring. Through this process, we particularly selected the homo mice and this transgenic line was used and maintained for this experiment.

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Mass spectrometry analysis of synaptic proteome of adult Fmr1 KO and wild-type mice.

Project description:Fragile X syndrome (FXS) is the most common monogenetic cause of inherited intellectual disability and autism in humans. One of the well-characterized molecular phenotypes of Fmr1 KO mice, a model of FXS, is increased translation of synaptic proteins. Although this upregulation stabilizes in the adulthood, abnormalities during the critical period of plasticity have long-term effects on circuit formation and synaptic properties. Using high-resolution quantitative proteomics of synaptoneurosomes isolated from the adult, developed brains of Fmr1 KO mice, we show differential abundance of proteins regulating postsynaptic receptor activity of glutamatergic synapse. This work includes proteomic dataset that was acquired and analyzed to quantify changes in the abundance of proteins in synaptoneurosomes (basal state, unstimulated and in vitro NMDA-R stimulated) isolated from Fmr1 KO mice and their wild-type littermates.

2024-01-26 | PXD043700 | Pride

C2C12 culture: myogenesis timecourse and shRp58 treatment

Project description:To predict Rp58-regulated gene involved in myogenesis, RNA profiling experiments were performed, comparing RNA derived from C2C12 with or without expressing shRNA for Rp58. As a result, 271 genes were upregulated in C2C12 stably expressing shRNA-Rp58 cells compared with control C2C12 cells. As Rp58 is repressor in C2C12, we hypothesized that Rp58 regulates gene cluster which expression is downregulated in accordance with Rp58 expression and myogenesis progression. In this regard, we also characterized dynamic gene expression patterns during myogenesis by microarray at 4 different stage (GM, day 0, 2, 4) of C2C12 myogenesis assays and found that 399 genes expression is characterized as downregulation pattern during myogenesis. Importantly, this down regulation gene set and upregulated genes by shRNA for Rp58 were highly overlapped. Keywords: time course, shRNA

2009-07-31 | GSE12993 | GEO

Metabolic Biomarkers of Ageing in C57BL/6J Wild-Type and Flavin-Containing Monooxygenase 5 (FMO5)-Knockout Mice

Project description:It was recently demonstrated in mice that knockout of the flavin-containing monooxygenase 5 gene, Fmo5, slows metabolic ageing via pleiotropic effects. We have now used an NMR-based metabonomics approach to study the effects of ageing directly on the metabolic profiles of urine and plasma from male, wild-type C57BL/6J and Fmo5−/− (FMO5 KO) mice back-crossed onto the C57BL/6J background. The aim of this study was to identify metabolic signatures that are associated with ageing in both these mouse lines and to characterize the age-related differences in the metabolite profiles between the FMO5 KO mice and their wild-type counterparts at equivalent time points. We identified a range of age-related biomarkers in both urine and plasma. Some metabolites, including urinary 6-hydroxy-6-methylheptan-3-one (6H6MH3O), a mouse sex pheromone, showed similar patterns of changes with age, regardless of genetic background. Others, however, were altered only in the FMO5 KO, or only in the wild-type mice, indicating the impact of genetic modifications on mouse ageing. Elevated concentrations of urinary taurine represent a distinctive, ageing-related change observed only in wild-type mice.

2018-06-20 | MTBLS667 | MetaboLights

Mus musculus

Project description:Brdt KO mice: Wild-type vs. Mutant

| PRJNA295068 | ENA