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dc.contributor.authorKe, F
dc.contributor.authorGrabow, S
dc.contributor.authorKelly, GL
dc.contributor.authorLin, A
dc.contributor.authorO'Reilly, LA
dc.contributor.authorStrasser, A
dc.date.accessioned2020-12-22T05:38:53Z
dc.date.available2020-12-22T05:38:53Z
dc.date.issued2015-10-01
dc.identifierpii: cddis2015304
dc.identifier.citationKe, F., Grabow, S., Kelly, G. L., Lin, A., O'Reilly, L. A. & Strasser, A. (2015). Impact of the combined loss of BOK, BAX and BAK on the hematopoietic system is slightly more severe than compound loss of BAX and BAK. CELL DEATH & DISEASE, 6 (10), https://doi.org/10.1038/cddis.2015.304.
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11343/258333
dc.description.abstractIt is well established that BAX and BAK play crucial, overlapping roles in the intrinsic pathway of apoptosis. Gene targeted mice lacking both BAX and BAK have previously been generated, but the majority of these animals died perinatally. BOK is a poorly studied relative of BAX and BAK that shares extensive amino acid sequence homology to both proteins, but its function remains largely unclear to date. To determine whether BOK plays an overlapping role with BAX and BAK, we utilized a hematopoietic reconstitution model where lethally irradiated wild type mice were transplanted with Bok(-/-)Bax(-/-)Bak(-/-) triple knockout (TKO) fetal liver cells, and compared alongside mice reconstituted with a Bax(-/-)Bak(-/-) double knockout (DKO) hematopoietic compartment. We report here that mice with a TKO and DKO hematopoietic system died at a similar rate and much earlier than control animals, mostly due to severe autoimmune pathology. Both TKO and DKO reconstituted mice also had altered frequencies of various leukocyte subsets in the thymus, bone marrow and spleen, displayed leukocyte infiltrates and autoimmune pathology in multiple tissues, as well as elevated levels of anti-nuclear autoantibodies. Interestingly, the additional deletion of BOK (on top of BAX and BAK loss) led to a further increase in peripheral blood lymphocytes, as well as enhanced lymphoid infiltration in some organs. These findings suggest that BOK may have some functions that are redundant with BAX and BAK in the hematopoietic system.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleImpact of the combined loss of BOK, BAX and BAK on the hematopoietic system is slightly more severe than compound loss of BAX and BAK
dc.typeJournal Article
dc.identifier.doi10.1038/cddis.2015.304
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleCell Death and Disease
melbourne.source.volume6
melbourne.source.issue10
dc.rights.licenseCC BY
melbourne.elementsid1039538
melbourne.contributor.authorGrabow, Stephanie
melbourne.contributor.authorStrasser, Andreas
melbourne.contributor.authorO'Reilly, Lorraine
melbourne.contributor.authorKe, Francine
melbourne.contributor.authorKelly, Gemma
dc.identifier.eissn2041-4889
melbourne.accessrightsOpen Access


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