BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development

Tools

Item Type:	Article
Title:	BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development
Creators Name:	Arsov, I., Li, X., Matthews, G., Coradin, J., Hartmann, B., Simon, A.K., Sealfon, S.C. and Yue, Z.
Abstract:	Beclin 1/Atg6 is an essential component of the evolutionary conserved PtdIns(3)-kinase (Vps34) protein complex that regulates macroautophagy (autophagy) in eukaryotic cells and also interacts with antiapoptotic Bcl-2 family members, Bcl-2, and Bcl-x(L). To elucidate the physiological function of Beclin 1, we generated transgenic mice producing a green fluorescent Beclin 1 protein (Beclin 1-GFP) under Beclin 1 endogenous regulation. The beclin 1-GFP transgene is functional because it completely rescues early embryonic lethality in beclin 1-deficient mice. The transgenic mice appear normal, with undetected change in basal autophagy levels in different tissues, despite the additional expression of functional Beclin 1-GFP. Staining of Beclin 1-GFP shows mostly diffuse cytoplasmic distribution in various tissues. Detailed analysis of the transgene expression by flow cytometry reveals a Bcl-2-like biphasic expression pattern in developing T and B cells, as well as differential regulation of expression in mature versus immature thymocytes following in vitro stimulation. Moreover, thymocytes expressing high Beclin 1-GFP levels appear increasingly sensitive to glucocorticoid-induced apoptosis in vitro. Our results, therefore, support a role for Beclin 1 in lymphocyte development involving cross talk between autophagy and apoptosis.
Keywords:	Beclin 1, Autophagy, T Cell, B Cell, Apoptosis, Animals, Mice
Source:	Cell Death and Differentiation
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Volume:	15
Number:	9
Page Range:	1385-95
Date:	September 2008
Official Publication:	https://doi.org/10.1038/cdd.2008.59
PubMed:	View item in PubMed

Repository Staff Only: item control page