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dc.contributor.authorWang, Wei
dc.contributor.authorHale, Christine
dc.contributor.authorGoulding, Dave
dc.contributor.authorHaslam, Stuart M
dc.contributor.authorTissot, Bérangère
dc.contributor.authorLindsay, Christopher
dc.contributor.authorMichell, Stephen
dc.contributor.authorTitball, Rick
dc.contributor.authorYu, Jun
dc.contributor.authorToribio, Ana Luisa
dc.contributor.authorRossi, Raffaella
dc.contributor.authorDell, Anne
dc.contributor.authorBradley, Allan
dc.contributor.authorDougan, Gordon
dc.date.accessioned2020-10-14T23:30:24Z
dc.date.available2020-10-14T23:30:24Z
dc.date.issued2011
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311499
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.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectalpha-Mannosidase
dc.subjectPolysaccharides
dc.subjectRicin
dc.subjectDNA Transposable Elements
dc.subjectSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
dc.subjectMutagenesis, Insertional
dc.subjectBase Sequence
dc.subjectGlycosylation
dc.subjectGene Library
dc.subjectMolecular Sequence Data
dc.subjectEmbryonic Stem Cells
dc.subjectGlycomics
dc.titleMannosidase 2, alpha 1 deficiency is associated with ricin resistance in embryonic stem (ES) cells.
dc.typeArticle
prism.issueIdentifier8
prism.publicationDate2011
prism.publicationNamePLoS One
prism.startingPagee22993
prism.volume6
dc.identifier.doi10.17863/CAM.58592
dcterms.dateAccepted2011-07-11
rioxxterms.versionofrecord10.1371/journal.pone.0022993
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2011-01
dc.contributor.orcidBradley, Allan [0000-0002-2349-8839]
dc.contributor.orcidDougan, Gordon [0000-0003-0022-965X]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Review
cam.issuedOnline2011-08-23


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International