Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment
Details
Publication Year 2017-03, Volume 24, Issue #3, Page 534-545
Journal Title
Cell Death and Differentiation
Publication Type
Journal Article
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 gammadeltaTCR 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.
Publisher
Springer Nature
WEHI Research Division(s)
Molecular Genetics Of Cancer; Immunology
PubMed ID
28085150
NHMRC Grants
NHMRC/1016701 NHMRC/1020363 NHMRC/1049720
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-04-12 10:42:22
Last Modified: 2017-04-12 11:33:11
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