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Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment
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Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment
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Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment
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Journal Article
Characterisation of mice lacking all functional isoforms of the pro-survival BCL-2 family member A1 reveals minor defects in the haematopoietic compartment
2017
Overview
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
γδ
TCR 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
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 631/250
/ 631/80
/ 64/60
/ Animals
/ Antigens
/ Biomedical and Life Sciences
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - metabolism
/ Dendritic Cells - metabolism
/ Intraepithelial Lymphocytes - cytology
/ Intraepithelial Lymphocytes - metabolism
/ Mice
/ Minor Histocompatibility Antigens - genetics
/ Minor Histocompatibility Antigens - metabolism
/ Myeloid Cell Leukemia Sequence 1 Protein - metabolism
/ Protein Isoforms - deficiency
/ Protein Isoforms - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
/ Proto-Oncogene Proteins c-bcl-2 - genetics
/ Proto-Oncogene Proteins c-bcl-2 - metabolism
