Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/746
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dc.contributor.authorPereira, Mafalda M. A.-
dc.contributor.authorMahú, Inês-
dc.contributor.authorSeixas, Elsa-
dc.contributor.authorMartinéz-Sánchez, Noelia-
dc.contributor.authorKubasova, Nadiya-
dc.contributor.authorPirzgalska, Roksana M-
dc.contributor.authorCohen, Paul-
dc.contributor.authorDietrich, Marcelo O-
dc.contributor.authorLópez, Miguel-
dc.contributor.authorBernardes, Gonçalo J. L.-
dc.contributor.authorDomingos, Ana I.-
dc.date.accessioned2017-04-10T14:21:49Z-
dc.date.available2017-04-10T14:21:49Z-
dc.date.issued2017-04-03-
dc.identifier.citationPereira, M. M. A. et al. A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages. Nat. Commun. 8, 14967 doi: 10.1038/ncomms14967 (2017).pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/746-
dc.description.abstractConditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood-brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood-brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system.pt_PT
dc.description.sponsorshipFundação para a Ciência e Tecnologia grant: (PTDC/BIM-MET/3750/2014); European Molecular Biology Organization (EMBO); European Community’s Seventh Framework Programme (FP7/2007-2013) under agreement no. (281854—the ObERStress project); MINECO co-funded by the FEDER Program of EU: (ML: SAF20015-71026-R); Xunta de Galicia grant: (ML: 2015-CP079); Instituto Gulbenkian de Ciência; Royal Society University.pt_PT
dc.language.isoengpt_PT
dc.publisherNature Publishing Grouppt_PT
dc.rightsopenAccesspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectChemical modificationpt_PT
dc.subjectMolecular neurosciencept_PT
dc.subjectNeuroimmunologypt_PT
dc.subjectPeripheral nervous systempt_PT
dc.titleA brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineagespt_PT
dc.typearticlept_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
degois.publication.firstPage1pt_PT
degois.publication.lastPage10pt_PT
degois.publication.titleNature Communicationspt_PT
dc.relation.publisherversionhttp://www.nature.com/articles/ncomms14967pt_PT
dc.peerreviewedyespt_PT
degois.publication.volume8pt_PT
dc.identifier.doi10.1038/ncomms14967pt_PT
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