Partial loss of interleukin 2 receptor gamma function in pigs provides mechanistic insights for the study of human immunodeficiency syndrome

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dc.contributor.authorChoi, Yun-Jungen
dc.contributor.authorLee, Kihoen
dc.contributor.authorPark, Woo-Jinen
dc.contributor.authorKwon, Deug-Namen
dc.contributor.authorPark, Chankyuen
dc.contributor.authorDo, Jeong Taeen
dc.contributor.authorSong, Hyuken
dc.contributor.authorCho, Seong-Keunen
dc.contributor.authorPark, Kwang-Wooken
dc.contributor.authorBrown, Alana N.en
dc.contributor.authorSamuel, Melissa S.en
dc.contributor.authorMurphy, Clifton N.en
dc.contributor.authorPrather, Randall S.en
dc.contributor.authorKim, Jin-Hoien
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2018-01-15T01:08:17Zen
dc.date.available2018-01-15T01:08:17Zen
dc.date.issued2016-08-09en
dc.description.abstractIn this study, we described the phenotype of monoallelic interleukin 2 receptor gamma knockout (mIL2RG+/Δ69-368 KO) pigs. Approximately 80% of mIL2RG+/Δ69-368 KO pigs (8/10) were athymic, whereas 20% (2/10) presented a rudimentary thymus. The body weight of IL2RG+/Δ69-368 KO pigs developed normally. Immunological analysis showed that mIL2RG+/Δ69-368 KO pigs possessed CD25+CD44- or CD25-CD44+ cells, whereas single (CD4 or CD8) or double (CD4/8) positive cells were lacking in mIL2RG+/Δ69-368 KO pigs. CD3+ cells in the thymus of mIL2RG+/Δ69-368 KO pigs contained mainly CD44+ cells and/or CD25+ cells, which included FOXP3+ cells. These observations demonstrated that T cells from mIL2RG+/Δ69-368 KO pigs were able to develop to the DN3 stage, but failed to transition toward the DN4 stage. Whole-transcriptome analysis of thymus and spleen, and subsequent pathway analysis revealed that a subset of genes differentially expressed following the loss of IL2RG might be responsible for both impaired T-cell receptor and cytokine-mediated signalling. However, comparative analysis of two mIL2RG+/Δ69-368 KO pigs revealed little variability in the down- and up-regulated gene sets. In conclusion, mIL2RG+/Δ69-368 KO pigs presented a T-B+NK- SCID phenotype, suggesting that pigs can be used as a valuable and suitable biomedical model for human SCID research.en
dc.description.versionPublished versionen
dc.format.extent50914 - 50926 (13) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.18632/oncotarget.10812en
dc.identifier.issn1949-2553en
dc.identifier.issue32en
dc.identifier.urihttp://hdl.handle.net/10919/81772en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000385429100014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en
dc.subjectOncologyen
dc.subjectCell Biologyen
dc.subjectIL2RGen
dc.subjectX-SCIDen
dc.subjectimmunodeficiencyen
dc.subjectsomatic cell nuclear transferen
dc.subjectTALENen
dc.subjectPathology Sectionen
dc.subjectCHAINen
dc.subjectCELLSen
dc.subjectLIVESTOCKen
dc.subjectKNOCKOUTen
dc.subjectGENESen
dc.titlePartial loss of interleukin 2 receptor gamma function in pigs provides mechanistic insights for the study of human immunodeficiency syndromeen
dc.title.serialOncotargeten
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen

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