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dc.contributor.authorWang, W
dc.contributor.authorHale, C
dc.contributor.authorGoulding, D
dc.contributor.authorHaslam, SM
dc.contributor.authorTissot, B
dc.contributor.authorLindsay, C
dc.contributor.authorMichell, S
dc.contributor.authorTitball, Richard W.
dc.contributor.authorYu, J
dc.contributor.authorToribio, AL
dc.contributor.authorRossi, R
dc.contributor.authorDell, A
dc.contributor.authorBradley, A
dc.contributor.authorDougan, G
dc.date.accessioned2013-06-04T13:46:19Z
dc.date.issued2011
dc.description.abstractHost gene products required for mediating the action of toxins are potential targets for reversing or controlling their pathogenic impact following exposure. To identify such targets libraries of insertional gene-trap mutations generated with a PiggyBac transposon in Blm-deficient embryonic stem cells were exposed to the plant toxin, ricin. Resistant clones were isolated and genetically characterised and one was found to be a homozygous mutant of the mannosidase 2, alpha 1 (Man2α1) locus with a matching defect in the homologous allele. The causality of the molecular lesion was confirmed by removal of the transposon following expression of PB-transposase. Comparative glycomic and lectin binding analysis of the Man2α1 (-/-) ricin resistant cells revealed an increase in the levels of hybrid glycan structures and a reduction in terminal β-galactose moieties, potential target receptors for ricin. Furthermore, naïve ES cells treated with inhibitors of the N-linked glycosylation pathway at the mannosidase 2, alpha 1 step exhibited either full or partial resistance to ricin. Therefore, we conclusively identified mannosidase 2, alpha 1 deficiency to be associated with ricin resistance.en_GB
dc.identifier.citationPLoS One, 2011, Vol. 6, Issue 8, pp. e22993en_GB
dc.identifier.doi10.1371/journal.pone.0022993
dc.identifier.otherPONE-D-10-04459
dc.identifier.urihttp://hdl.handle.net/10871/9834
dc.language.isoenen_GB
dc.publisherPublic Library of Scienceen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21886775en_GB
dc.relation.urlhttp://www.plosone.org/article/info:doi/10.1371/journal.pone.0022993en_GB
dc.subjectBase Sequenceen_GB
dc.subjectCell Lineen_GB
dc.subjectDNA Transposable Elementsen_GB
dc.subjectEmbryonic Stem Cellsen_GB
dc.subjectGene Libraryen_GB
dc.subjectGlycomicsen_GB
dc.subjectGlycosylationen_GB
dc.subjectMolecular Sequence Dataen_GB
dc.subjectMutagenesis, Insertionalen_GB
dc.subjectPolysaccharidesen_GB
dc.subjectRicinen_GB
dc.subjectSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationen_GB
dc.subjectalpha-Mannosidaseen_GB
dc.titleMannosidase 2, alpha 1 deficiency is associated with ricin resistance in embryonic stem (ES) cells.en_GB
dc.typeArticleen_GB
dc.date.available2013-06-04T13:46:19Z
exeter.place-of-publicationUnited States
dc.descriptionaddresses: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.en_GB
dc.descriptionnotes: PMCID: PMC3160287en_GB
dc.descriptiontypes: Journal Article; Research Support, Non-U.S. Gov'ten_GB
dc.descriptionCopyright: © 2011 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_GB
dc.identifier.journalPLoS Oneen_GB


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