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

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

  • Schenk, Robyn L
  • Tuzlak, Selma
  • Carrington, Emma M
  • Zhan, Yifan
  • Heinzel, Susanne
  • Teh, Charis E
  • Gray, Daniel H
  • Tai, Lin
  • Lew, Andrew M
  • Villunger, Andreas
  • Strasser, Andreas
  • Herold, Marco J

publication date

  • 2017

has subject area