MOG1

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant...

The RAN Guanine Nucleotide Release Factor (RANGRF) gene encodes the protein MOG1, which binds to Nav1.5 and facilitates its transport to the cell membrane. Nav1.5 mutations have been linked to various cardiac arrhythmias and cardiomyopathy. To investigate the role of RANGRF in this process, we utilized the CRISPR/Cas9 gene editing system to generate a homozygous RANGRF knockout hiPSC line. The availability of the cell line will prove to be an invaluable asset in the study of disease mechanisms and the testing of gene therapies for cardiomyopathy...

Experimental autoimmune encephalomyelitis (EAE) is an animal model of Inflammatory central nervous system (CNS) disease. Dark agouti (DA) rats immunized with full-length myelin oligodendrocyte glycoprotein (MOG1-125 ) typically develop a relapsing-remitting EAE form characterized by predominant demyelinating involvement of the spinal cord and optic nerve. Visually evoked potentials (VEP) are a useful objective tool to assess the optic nerve function and monitor electrophysiological changes in optic neuritis (ON)...

In order to investigate the salt stress induced chlorophyll biosynthesis-related genes in photoheterotrophic cultures, we performed RNA-Seq analysis on A. thaliana calli exposed to 100 mM NaCl on MS medium containing 0.5 mg/L 2,4-D 30 days. Four different conditions of samples were sequenced on Illumina HiSeq Platform in total and generated about 4.49 Gb per sample. The average genome and gene mapping rates were 93.52% and 90.78%, respectively. According to expression profile analysis, some DEGs demonstrated altered related to chlorophyll pigment metabolism...

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system with no cure yet. Here, we report genetic engineering of hematopoietic stem cells (HSCs) to express myelin oligodendrocyte glycoprotein (MOG), specifically in platelets, as a means of intervention to induce immune tolerance in experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. The platelet-specific αIIb promoter was used to drive either a full-length or truncated MOG expression cassette. Platelet-MOG expression was introduced by lentivirus transduction of HSCs followed by transplantation...

Up to 92% of patients suffering from multiple sclerosis (MS) experience pain, most without adequate treatment, and many report pain long before motor symptoms associated with MS diagnosis. In the most commonly studied rodent model of MS, experimental autoimmune encephalomyelitis (EAE), motor impairments/disabilities caused by EAE can interfere with pain testing. In this study, we characterize a novel low-dose myelin-oligodendrocyte-glycoprotein (MOG)-induced Sprague-Dawley (SD) model of EAE-related pain in male rats, optimized to minimize motor impairments/disabilities...

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate-limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development...

Brugada syndrome (BrS) is a fatal arrhythmia that causes an estimated 4% of all sudden death in high-incidence areas. SCN5A encodes cardiac sodium channel NaV 1.5 and causes 25 to 30% of BrS cases. Here, we report generation of a knock-in (KI) mouse model of BrS ( Scn5aG1746R/+ ). Heterozygous KI mice recapitulated some of the clinical features of BrS, including an ST segment abnormality (a prominent J wave) on electrocardiograms and development of spontaneous ventricular tachyarrhythmias (VTs), seizures, and sudden death...

Our earlier studies identified MOG1 as a Nav1.5-binding protein that promotes Nav1.5 intracellular trafficking to plasma membranes. Genetic studies have identified MOG1 variants responsible for cardiac arrhythmias. However, the physiological functions of MOG1 in vivo remain incompletely characterized. In this study, we generated Mog1 knockout (Mog1-/- ) mice. Mog1-/- mice did not develop spontaneous arrhythmias at the baseline, but exhibited a prolongation of QRS duration. Mog1-/- mice treated with isoproterenol (ISO), but not with flecainide, exhibited an increased risk of arrhythmias and even sudden death...

BACKGROUND: Mutations in cardiac sodium channel Nav 1.5 cause Brugada syndrome (BrS). MOG1 is a chaperone that binds to Nav 1.5, facilitates Nav 1.5 trafficking to the cell surface, and enhances the amplitude of sodium current INa . OBJECTIVE: The purpose of this study was to identify structural elements involved in MOG1-Nav 1.5 interaction and their relevance to the pathogenesis of BrS. METHODS: Systematic analyses of large deletions, microdeletions, and point mutations, and glutathione S-transferases pull-down, co-immunoprecipitation, cell surface protein quantification, and patch-clamping of INa were performed...

Two pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and remyelination in multiple sclerosis, and the experimental autoimmune encephalomyelitis (EAE, MOG1-125) immune-mediated events. The frontal cortex, peripheral to severely inflicted areas in the CNS, was dissected and analyzed...

Myelin oligodendrocyte glycoprotein is a transmembrane protein found on the outer lamella of the myelin sheath. The autoimmune attack on the MOG leads to demyelination which differs from normal multiple sclerosis. MOG has three epitope regions MOG1-22 , MOG35-55 , and MOG92-106 in the extracellular region, and the crucial MOG35-55 epitope and Human Leukocyte Antigen (HLA) interaction is the initial step for autoantibody generation. To study the effective role of glycosylation in MOG-HLA interaction, we performed molecular dynamics simulations of the complex where HLA interacts with three MOG epitopes both in the absence and presence of glycan...

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AIMS: MOG1 is a small protein that can bind to small GTPase RAN and regulate transport of RNA and proteins between the cytoplasm and nucleus. However, the in vivo physiological role of mog1 in the heart needs to be fully defined. METHODS: Mog1 knockout zebrafish was generated by TALEN. Echocardiography, histological analysis, and electrocardiograms were used to examine cardiac structure and function. RNA sequencing and real-time RT-PCR were used to elucidate the molecular mechanism and to analyse the gene expression...

BACKGROUND: B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE)...

Trigeminal neuralgia is often an early symptom of multiple sclerosis (MS), and it generally does not correlate with the severity of the disease. Thus, whether it is triggered simply by demyelination in specific central nervous system areas is currently questioned. Our aims were to monitor the development of spontaneous trigeminal pain in an animal model of MS, and to analyze: i) glial cells, namely astrocytes and microglia in the central nervous system and satellite glial cells in the trigeminal ganglion, and ii) metabolic changes in the trigeminal system...

Ethanol tolerance, a polygenic trait of the yeast Saccharomyces cerevisiae , is the primary factor determining industrial bioethanol productivity. Until now, genomic elements affecting ethanol tolerance have been mapped only at low resolution, hindering their identification. Here, we explore the genetic architecture of ethanol tolerance, in the F6 generation of an Advanced Intercrossed Line (AIL) mapping population between two phylogenetically distinct, but phenotypically similar, S. cerevisiae strains (a common laboratory strain and a wild strain isolated from nature)...

BACKGROUND: Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3). Mutations in SCN5A gene coding for the α-subunit of the NaV1.5 cardiac sodium channel are identified in 15-30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of the protein-coding portions and flanking intronic regions of SCN5A...

Nav 1.5 is the α-subunit of the cardiac sodium channel complex. Abnormal expression of Nav 1.5 on the cell surface because of mutations that disrupt Nav 1.5 trafficking causes Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction disease, dilated cardiomyopathy, and sudden infant death syndrome. We and others previously reported that Ran-binding protein MOG1 (MOG1), a small protein that interacts with Nav 1.5, promotes Nav 1.5 intracellular trafficking to plasma membranes and that a substitution in MOG1, E83D, causes BrS...

BACKGROUND: The cardiac sodium channel Nav 1.5 is essential for the physiological function of the heart and causes cardiac arrhythmias and sudden death when mutated. Many disease-causing mutations in Nav 1.5 cause defects in protein trafficking, a cellular process critical to the targeting of Nav 1.5 to cell surface. However, the molecular mechanisms underlying the trafficking of Nav 1.5, in particular, the exit from the endoplasmic reticulum (ER) for cell surface trafficking, remain poorly understood...