title: Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice.
abstract: The pro-apoptotic BH3-only BCL-2 family member BIM is a critical determinant of hematopoietic cell development and homeostasis. It has been argued that the striking hematopoietic abnormalities of BIM-deficient mice (accumulation of lymphocytes and granulocytes) may be the result of the loss of the protein throughout the whole animal rather than a consequence intrinsic to the loss of BIM in hematopoietic cells. To address this issue and allow the deletion of BIM in specific cell types in future studies, we have developed a mouse strain with a conditional Bim allele as well as a new Cre transgenic strain, Vav-CreER, in which the tamoxifen-inducible CreER recombinase (fusion protein) is predominantly expressed in the hematopoietic system. We show that acute loss of BIM in the adult mouse rapidly results in the hematopoietic phenotypes previously observed in mice lacking BIM in all tissues. This includes changes in thymocyte subpopulations, increased white blood cell counts and resistance of lymphocytes to BIM-dependent apoptotic stimuli, such as cytokine deprivation. We have validated this novel conditional Bim knockout mouse model using established and newly developed CreER strains (Rosa26-CreER and Vav-CreER) and will make these exciting new tools for studies on cell death and cancer available.
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Herold
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Stuchbery
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Mérino
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Willson
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.affiliation: Division of Cellular and Molecular Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hildeman
authors.affiliation: 1] Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Bouillet
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D017353:Gene Deletion; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins