title: Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment.
abstract: The pro-survival proteins of the BCL-2 family regulate the survival of all cells, and genetic deletion models for these proteins have revealed which specific BCL-2 family member(s) is/are critical for the survival of particular cell types. A1 is a pro-survival BCL-2-like protein that is expressed predominantly in haematopoietic cells, and here we describe the characterisation of a novel mouse strain that lacks all three functional isoforms of A1 (A1-a, A1-b and A1-d). Surprisingly, complete loss of A1 caused only minor defects, with significant, although relatively small, decreases in γδTCR T cells, antigen-experienced conventional as well as regulatory CD4 T cells and conventional dendritic cells (cDCs). When examining these cell types in tissue culture, only cDC survival was significantly impaired by the loss of A1. Therefore, A1 appears to be a surprisingly redundant pro-survival protein in the haematopoietic system and other tissues, suggesting that its targeting in cancer may be readily tolerated.
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Schenk
authors.affiliation: Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.|Divison of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Selma
authors.initials: S
authors.lastname: Tuzlak
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Carrington
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Susanne
authors.identifier: 0000-0001-9524-2835
authors.initials: S
authors.lastname: Heinzel
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Charis E
authors.initials: CE
authors.lastname: Teh
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Gray
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Tai
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.affiliation: Divison of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.|Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Villunger
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Herold
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D000075942:Intraepithelial Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D000066450:Mouse Embryonic Stem Cells; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051020:bcl-X Protein