0000000000235004

AUTHOR

Martin Hrabě De Angelis

showing 3 related works from this author

Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.

2019

Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…

Malemedicine.medical_specialtyOffspring610 Medicine & healthHemorrhage030204 cardiovascular system & hematologyBiologymedicine.disease_causeArticleThromboplastin11459 Center for Molecular Cardiology03 medical and health sciencesTissue factorArterial Thrombosis; Blood Coagulation and Fibrinolysis; Disorders of Coagulation and FibrinolysisMice0302 clinical medicineIn vivoPregnancyInternal medicinemedicineExtracellularAnimalsDisulfidesMutationHematologyPhenotypeIn vitroEndocrinologyPhenotype10036 Medical Clinic10076 Center for Integrative Human PhysiologyHemostasisMutation10209 Clinic for CardiologyFemale030215 immunologyHaematologica
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Functional Inactivation of the Genome-Wide Association Study Obesity Gene Neuronal Growth Regulator 1 in Mice Causes a Body Mass Phenotype

2012

To date, genome-wide association studies (GWAS) have identified at least 32 novel loci for obesity and body mass-related traits. However, the causal genetic variant and molecular mechanisms of specific susceptibility genes in relation to obesity are yet to be fully confirmed and characterised. Here, we examined whether the candidate gene NEGR1 encoding the neuronal growth regulator 1, also termed neurotractin or Kilon, accounts for the obesity association. To characterise the function of NEGR1 for body weight control in vivo, we generated two novel mutant mouse lines, including a constitutive NEGR1-deficient mouse line as well as an ENU-mutagenised line carrying a loss-of-function mutation …

MaleCandidate geneMutantlcsh:MedicineGenome-wide association studymedicine.disease_causeEndoplasmic ReticulumEatingGene Knockout TechniquesMice0302 clinical medicineEndocrinologylcsh:ScienceObesity; NEGR1; GWAS; body weight control2. Zero hungerGenetics0303 health sciencesMutationMultidisciplinaryNeuronal growth regulator 1GenomicsPhenotypePhenotypeMedicineFemaleFunction and Dysfunction of the Nervous SystemResearch ArticleGenotypeHypothalamusNerve Tissue ProteinsBiologyMotor ActivityDiet High-FatCell Line03 medical and health sciencesGenetic MutationGenome Analysis ToolsmedicineGeneticsGenome-Wide Association StudiesCell AdhesionNeuritesAnimalsHumansObesityGene SilencingGeneBiologyAlleles030304 developmental biologyNutritionlcsh:RBody WeightMembrane ProteinsHuman GeneticsNeuroendocrinologyBody HeightMetabolic DisordersGenetics of DiseaseLean body masslcsh:QEnergy Metabolism030217 neurology & neurosurgeryGenome-Wide Association StudyPLoS ONE
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Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia.

2018

Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression. Therefore, up-regulation of Faim2 may contribute to neuroprotection by EPO. Male Faim…

Male0301 basic medicinemetabolism [Apoptosis Regulatory Proteins]FAIM2 protein humanlifeguard protein mouseIschemiaNerve Tissue Proteinspathology [Ischemic Attack Transient]physiology [Neuroprotection]PharmacologyBiochemistryNeuroprotectionmetabolism [Erythropoietin]metabolism [Ischemic Attack Transient]Brain ischemiaMice03 medical and health sciencesCellular and Molecular Neuroscience0302 clinical medicinemedicineAnimalsHumansddc:610ErythropoietinStrokeProtein kinase BPI3K/AKT/mTOR pathwayAgedpharmacology [Erythropoietin]Mice Knockoutmetabolism [Nerve Tissue Proteins]business.industryPenumbraMembrane ProteinsMiddle Agedmedicine.diseaseNeuroprotection030104 developmental biologyIschemic Attack TransientErythropoietinphysiopathology [Ischemic Attack Transient]FemaleDose-dependency ; Erythropoietin ; Fas-apoptotic Inhibitory Molecule 2 ; Ischemia-reperfusion ; Neuroprotection ; StrokeApoptosis Regulatory Proteinsbusinessmetabolism [Membrane Proteins]030217 neurology & neurosurgerymedicine.drug
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