Now showing 1 - 4 of 4
  • 2021Journal Article Research Paper
    [["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Dörje, Nele M."],["dc.contributor.author","Bahader, Iman"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Thirumalai, Anupriya"],["dc.contributor.author","Weber, Thomas"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (\\u0026lt;5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches."],["dc.identifier.doi","10.3389/fnmol.2020.600051"],["dc.identifier.pmid","33488357"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83002"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/123"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]
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  • 2020Journal Article Research Paper
    [["dc.bibliographiccitation.firstpage","8758"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.affiliation","Voorn, Roos Anouk; \t\t \r\n\t\t Presynaptogenesis and Intracellular Transport in Hair Cells Junior Research Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Goettingen, 37075 Goettingen, Germany, roosanouk.voorn@med.uni-goettingen.de\t\t \r\n\t\t Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences, 37075 Goettingen, Germany, roosanouk.voorn@med.uni-goettingen.de\t\t \r\n\t\t Collaborative Research Center 889 “Cellular Mechanisms of Sensory Processing”, 37075 Goettingen, Germany, roosanouk.voorn@med.uni-goettingen.de"],["dc.contributor.affiliation","Vogl, Christian; \t\t \r\n\t\t Presynaptogenesis and Intracellular Transport in Hair Cells Junior Research Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Goettingen, 37075 Goettingen, Germany, christian.vogl@med.uni-goettingen.de\t\t \r\n\t\t Collaborative Research Center 889 “Cellular Mechanisms of Sensory Processing”, 37075 Goettingen, Germany, christian.vogl@med.uni-goettingen.de"],["dc.contributor.author","Voorn, Roos Anouk"],["dc.contributor.author","Vogl, Christian"],["dc.date.accessioned","2021-04-14T08:31:05Z"],["dc.date.available","2021-04-14T08:31:05Z"],["dc.date.issued","2020"],["dc.date.updated","2022-09-06T17:44:57Z"],["dc.identifier.doi","10.3390/ijms21228758"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83482"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Molecular Assembly and Structural Plasticity of Sensory Ribbon Synapses—A Presynaptic Perspective"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2021Journal Article Research Paper
    [["dc.bibliographiccitation.artnumber","651935"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Burfeind, Dinah"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Krinner, Stefanie"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Vogl, Christian"],["dc.date.accessioned","2021-04-29T08:36:41Z"],["dc.date.available","2021-04-29T08:36:41Z"],["dc.date.issued","2021"],["dc.description.abstract","The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 - multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and Ca V 1.3 - in IHC presynaptic function and hearing. Recordings of auditory brainstem responses and otoacoustic emissions revealed that genetic disruption of RIM-BPs 1 and 2 in mice (RIM-BP1/2-/- ) causes a synaptopathic hearing impairment exceeding that found in mice lacking RIM-BP2 (RIM-BP2-/- ). Patch-clamp recordings from RIM-BP1/2-/- IHCs indicated a subtle impairment of exocytosis from the readily releasable pool of synaptic vesicles that had not been observed in RIM-BP2-/- IHCs. In contrast, the reduction of Ca2+-influx and sustained exocytosis was similar to that in RIMBP2-/- IHCs. We conclude that both RIM-BPs are required for normal sound encoding at the IHC synapse, whereby RIM-BP2 seems to take the leading role."],["dc.identifier.doi","10.3389/fnmol.2021.651935"],["dc.identifier.pmid","33867935"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84562"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/237"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/114"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B05: Quantitative molekulare Physiologie aktiver Zonen in Calyx-Synapsen"],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]
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  • 2018Journal Article Research Paper
    [["dc.bibliographiccitation.firstpage","139"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The EMBO journal"],["dc.bibliographiccitation.lastpage","159"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Richter, Katharina N."],["dc.contributor.author","Revelo, Natalia H."],["dc.contributor.author","Seitz, Katharina J."],["dc.contributor.author","Helm, Martin S."],["dc.contributor.author","Sarkar, Deblina"],["dc.contributor.author","Saleeb, Rebecca S."],["dc.contributor.author","d'Este, Elisa"],["dc.contributor.author","Eberle, Jessica"],["dc.contributor.author","Wagner, Eva"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Richter, Frank"],["dc.contributor.author","Coy-Vergara, Javier"],["dc.contributor.author","Coceano, Giovanna"],["dc.contributor.author","Boyden, Edward S."],["dc.contributor.author","Duncan, Rory R."],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Lauterbach, Marcel A."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Schwappach, Blanche"],["dc.contributor.author","Testa, Ilaria"],["dc.contributor.author","Zapiec, Bolek"],["dc.contributor.author","Rizzoli, Silvio O."],["dc.date.accessioned","2018-01-09T14:09:53Z"],["dc.date.available","2018-01-09T14:09:53Z"],["dc.date.issued","2018"],["dc.description.abstract","Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining."],["dc.identifier.doi","10.15252/embj.201695709"],["dc.identifier.pmid","29146773"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15063"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11599"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/195"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/15"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P09: Proteinsortierung in der Synapse: Prinzipien und molekulare Organisation"],["dc.relation.eissn","1460-2075"],["dc.relation.workinggroup","RG Hell"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Schwappach (Membrane Protein Biogenesis)"],["dc.relation.workinggroup","RG Rizzoli (Quantitative Synaptology in Space and Time)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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