Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment.
Cell Death Differ
; 24(3): 534-545, 2017 03.
Article
in En
| MEDLINE
| ID: mdl-28085150
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Minor Histocompatibility Antigens
/
Proto-Oncogene Proteins c-bcl-2
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cell Death Differ
Year:
2017
Document type:
Article
Affiliation country: