Journal article
Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial Abnormalities
S Grabow, AJ Kueh, F Ke, HK Vanyai, BN Sheikh, MA Dengler, W Chiang, S Eccles, IM Smyth, LK Jones, FJ de Sauvage, M Scott, L Whitehead, AK Voss, A Strasser
Cell Reports | CELL PRESS | Published : 2018
Abstract
Apoptotic cell death removes unwanted cells and is regulated by interactions between pro-survival and pro-apoptotic members of the BCL-2 protein family. The regulation of apoptosis is thought to be crucial for normal embryonic development. Accordingly, complete loss of pro-survival MCL-1 or BCL-XL (BCL2L1) causes embryonic lethality. However, it is not known whether minor reductions in pro-survival proteins could cause developmental abnormalities. We explored the rate-limiting roles of MCL-1 and BCL-XL in development and show that combined loss of single alleles of Mcl-1 and Bcl-x causes neonatal lethality. Mcl-1+/–;Bcl-x+/– mice display craniofacial anomalies, but additional loss of a singl..
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Awarded by Human Frontier Science Program
Funding Acknowledgements
We thank Drs. P. Bouillet, L. Hennighausen, and S.J. Korsmeyer for mice; J. Mansheim, S.O'Connor, S. Allan, C.D'Alessando, K. Landells, and G. Siciliano for expert animal care; L.A. O'Reilly for antibodies; E. Tsui, C. Tsui, V. Orlando, K. Weston, and Y. Hoang for histology services; and D. Anbarci for taking pictures of the histological slides for analysis and in situ preparations under the guidance of H. K.V. This work was supported by grants and fellowships from the Cancer Council of Victoria (S.G., F.K.), the Lady Tata Memorial Trust (S.G. and F.K.), the Leukaemia Foundation Australia (S.G.), the Australian Research Council (DP10310086 and Future Fellowship FT100100620 to I.M.S.), the Human Frontiers in Science Program (RGP0039/2011 to I.M.S.), the National Health and Medical Research Council (NHMRC) (Program Grant 1016701; NHMRC Fellowships 1020363 to A.S. and 575512 and 1081421 to A.K.V.; Project Grant 1051078 to A.K.V.), the Leukemia and Lymphoma Society (SCOR Grant 7001-03 to A.S.), a University of Melbourne International Research Scholarship (to S.G.), a University of Melbourne International Fee Remission Scholarship (to S.G.), an Australian Post-graduate Award (to H.K.V.), a Cancer Therapeutics CRC Top-Up Scholarship (to S.G.), and operational infrastructure grants through the Australian Government Independent Medical Research Institutes Infrastructure Support Scheme (IRIISS) and the Victorian State Government Operational Infrastructure Support (OIS) Program.