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Cell Death Differ. 2017 Mar;24(3):534-545. doi: 10.1038/cdd.2016.156. Epub 2017 Jan 13.

Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment.

Author information

1
The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.
2
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
3
Divison of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.
4
Tyrolean Cancer Research Institute, Innsbruck, Austria.

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.

PMID:
28085150
PMCID:
PMC5344213
DOI:
10.1038/cdd.2016.156
[Indexed for MEDLINE]
Free PMC Article

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