0000000000380759

AUTHOR

Nadine Mersmann

showing 3 related works from this author

Aspartoacylase-lacZ knockin mice: an engineered model of Canavan disease.

2011

Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspa(lacZ/+)) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (…

MaleCentral Nervous SystemCerebellumPathologyAnatomy and PhysiologyCanavan DiseaseMouseMutantlcsh:MedicineNeural HomeostasisBiochemistryMiceNeurobiology of Disease and Regenerationlcsh:ScienceSex CharacteristicsMultidisciplinaryNeuromodulationNeurochemistryGenomicsAnimal ModelsFunctional Genomicsmedicine.anatomical_structureLac OperonNeurologyHomeostatic MechanismsMedicineFemaleNeurochemicalsGenetic EngineeringResearch ArticleNervous System PhysiologyBiotechnologymedicine.medical_specialtyTransgeneCentral nervous systemNeurophysiologyMice TransgenicNeuroimagingBiologyNeurological SystemAmidohydrolasesWhite matterModel OrganismsGeneticsmedicineAnimalsBiologyNeuropeptidesLeukodystrophylcsh:RComputational Biologymedicine.diseaseMolecular biologyCanavan diseaseAspartoacylaseDisease Models AnimalMetabolismnervous systemSmall MoleculesCellular NeuroscienceMetabolic DisordersMutationGenetics of DiseaseNervous System Componentslcsh:QGene FunctionMolecular NeuroscienceAnimal GeneticsNeurosciencePLoS ONE
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Glial Promoter Selectivity following AAV-Delivery to the Immature Brain

2013

Recombinant adeno-associated virus (AAV) vectors are versatile tools for gene transfer to the central nervous system (CNS) and proof-of-concept studies in adult rodents have shown that the use of cell type-specific promoters is sufficient to target AAV-mediated transgene expression to glia. However, neurological disorders caused by glial pathology usually have an early onset. Therefore, modelling and treatment of these conditions require expanding the concept of targeted glial transgene expression by promoter selectivity for gene delivery to the immature CNS. Here, we have investigated the AAV-mediated green fluorescent protein (GFP) expression driven by the myelin basic protein (MBP) or gl…

MouseCanavan DiseaseGene ExpressionDevelopmental and Pediatric NeurologyPediatricsGreen fluorescent protein0302 clinical medicineGene expressionNeurobiology of Disease and RegenerationTransgenesPromoter Regions GeneticCells Cultured0303 health sciencesMultidisciplinaryGlial fibrillary acidic proteinQStatisticsRAge FactorsBrainGenomicsGene TherapyAnimal ModelsDependovirusOligodendrogliamedicine.anatomical_structureNeurologyOrgan SpecificityMedicineGenetic EngineeringResearch ArticleBiotechnologyScienceTransgeneCentral nervous systemGenetic VectorsGreen Fluorescent ProteinsGene deliveryBiologyBiostatistics03 medical and health sciencesModel OrganismsGenomic MedicineDevelopmental NeuroscienceNeuroglial DevelopmentGlial Fibrillary Acidic ProteinmedicineGeneticsAnimalsBiology030304 developmental biologyClinical GeneticsMyelin Basic ProteinGenetic TherapyMolecular biologyOligodendrocyteMyelin basic proteinMice Inbred C57BLAnimals NewbornAstrocytesbiology.protein030217 neurology & neurosurgeryMathematicsTransgenicsNeurosciencePLoS ONE
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Aav-based gene therapy approaches for the treatment of canavan disease

2013

Background: The enzyme Aspartoacylase (ASPA) is normally expressed in oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). ASPA gene mutations cause Canavan Disease (CD), a devastating neurological disorder characterized by psychomotor retardation, and spongiform degeneration of central white matter in affected children. The lack of ASPA leads to the enrichment in its substrate N-acetyl aspartate (NAA) which is a biomarker of CD. With no available treatment and a pathology restricted to the CNS CD has been trialled by gene therapy. However, gene replacement approaches using neurotropic recombinant adeno-associated viral (rAAV) vectors have proved unsuccessful. It …

Cancer ResearchTransplantationbiologyTransgeneGenetic enhancementImmunologyCell BiologyGene mutationmedicine.diseaseMolecular biologyCanavan diseaseAspartoacylaseMyelin basic proteinMyelinmedicine.anatomical_structurenervous systemOncologymedicinebiology.proteinImmunology and AllergyVector (molecular biology)Genetics (clinical)Cytotherapy
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