| First Author | Wang W | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 8 | Pages | e22993 |
| PubMed ID | 21886775 | Mgi Jnum | J:176343 |
| Mgi Id | MGI:5291520 | Doi | 10.1371/journal.pone.0022993 |
| Citation | Wang W, et al. (2011) Mannosidase 2, alpha 1 Deficiency Is Associated with Ricin Resistance in Embryonic Stem (ES) Cells. PLoS One 6(8):e22993 |
| abstractText | 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 (Man2alpha1) 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 Man2alpha1 (-/-) ricin resistant cells revealed an increase in the levels of hybrid glycan structures and a reduction in terminal beta-galactose moieties, potential target receptors for ricin. Furthermore, naive 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. |
