Journal article
Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease
KD Mason, A Lin, L Robb, EC Josefsson, KJ Henley, DHD Gray, BT Kile, AW Roberts, A Strasser, DCS Huang, P Waring, LA O'Reilly
Proceedings of the National Academy of Sciences of the United States of America | Published : 2013
Abstract
Dysregulation of the "intrinsic" apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak-/- bax-/- mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doub..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank C. Thompson (Memorial Sloan-Kettering Cancer Center, New York) for bak<SUP>-/-</SUP> mice; the late S. Korsmeyer (Harvard University) for bax<SUP>-/-</SUP> mice; L. Lee for technical assistance; G. Siciliano, J. Coughlin, K. McKenzie, F. Dabrowski, S. Ross, S. Green, C. Evans, K. Trueman, E. Lanera, H. Donatucci, and D. Cooper for animal care; J. Corbin for automated blood analysis; B. Helbert, C. Young, and A. Georgiou for genotyping; and S. Mihajlovic, E. Tsui, A. Hasanein, V. Babo, and K. Weston for preparation of histological sections. This work was supported by fellowships and grants from the National Health and Medical Research Council (NHMRC) [Canberra; programs 461221, 461219, fellowships; Australia Fellowship (to A.S.), 637353 (to D.H.D.G.), 516701; and Project Grant 637309 (to A.W.R.), 575535 (to B.T.K.), 637332 (to D.H.D.G.), and 1009145 (to L.A.O.)], an NHMRC infrastructure grant, Independent Research Institutes Infrastructure Support Scheme Grant 361646, the Victorian State Government Operational Infrastructure Support (OIS) grant, the Leukemia and Lymphoma Society [Specialized Centre of Research (SCOR) Grant 7413, fellowship to E.C.J.], National Institutes of Health Grants CA043540-18 and CA80188-6, the Juvenile Diabetes Research Fund (JDRF)/NHMRC (A.S.), the Association for International Cancer Research, the Victorian Cancer Agency (K.D.M. and A.W.R.), the Australian Cancer Research Foundation, the Sylvia and Charles Viertel Charitable Foundation, and the Leukemia Foundation Australia (B.T.K.).