Journal article

Combined reduction in the expression of MCL-1 and BCL-2 reduces organismal size in mice

Francine Ke, Graeme Lancaster, Stephanie Grabow, Andrew J Murphy, Andreas Strasser

Cell Death and Disease | NATURE PUBLISHING GROUP | Published : 2020


The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins have also been identified. In the process of studying mice lacking single alleles of Mcl-1 (Mcl-1+/-), Bcl-2 (Bcl-2+/-), or both in combination (Mcl-1+/-Bcl-2+/-), we observed that Mcl-1+/-Bcl-2+/- mice weighed less when compared with their wild-type littermates as they aged. Body composition analysis demonstrated that while fat mass was similar to wild-type controls, lean mass ..

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank Drs. P. Bouillet and S. Korsmeyer for gifts of mice; G. Siciliano, A. Coad, C. Stivala and the AMREP precinct animal facility for animal care; K. Weston for blood cell analysis; B. Helbert and R. Chan for genotyping and the WEHI histology facility for histological preparations. This work was supported by grants and fellowships from the Leukaemia Foundation Australia (to F.K., S.G.), Cancer Council Victoria (to F.K., S.G.), Lady Tata Memorial Trust International Research Award (to S.G.) and the National Health and Medical Research Council (Program Grant #1016701, Project grant #1086291, Fellowship #1020363; all to A.S.). This work was made possible by the operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.