dc.contributor.author | Wang, W | |
dc.contributor.author | Hale, C | |
dc.contributor.author | Goulding, D | |
dc.contributor.author | Haslam, SM | |
dc.contributor.author | Tissot, B | |
dc.contributor.author | Lindsay, C | |
dc.contributor.author | Michell, S | |
dc.contributor.author | Titball, Richard W. | |
dc.contributor.author | Yu, J | |
dc.contributor.author | Toribio, AL | |
dc.contributor.author | Rossi, R | |
dc.contributor.author | Dell, A | |
dc.contributor.author | Bradley, A | |
dc.contributor.author | Dougan, G | |
dc.date.accessioned | 2013-06-04T13:46:19Z | |
dc.date.issued | 2011-08-23 | |
dc.description.abstract | Host 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.citation | Vol. 6, Issue 8, article e22993 | en_GB |
dc.identifier.doi | 10.1371/journal.pone.0022993 | |
dc.identifier.uri | http://hdl.handle.net/10871/9834 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/21886775 | en_GB |
dc.title | Mannosidase 2, alpha 1 deficiency is associated with ricin resistance in embryonic stem (ES) cells | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2013-06-04T13:46:19Z | |
exeter.place-of-publication | United States | |
dc.description | Copyright: © 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.journal | PLoS One | en_GB |