Loss of BH3-only protein bim inhibits apoptosis of hemopoietic cells in the fetal liver and male germ cells but not neuronal cells in Bcl-x-deficient mice

Akhtar, RS; Klocke, BJ; Strasser, A; Roth, KA

Author(s): Akhtar, RS; Klocke, BJ; Strasser, A; Roth, KA;
Details: Publication Year 2008-10,Volume 56,Issue #10,Page 921-927
Journal Title: JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Publication Type: Journal Article
Abstract: Members of the Bcl-2 family include pro- and antiapoptotic proteins that regulate programmed cell death of developing tissues and death in response to cellular damage. In developing mice, the antiapoptotic Bcl-x(L) is necessary for survival of neural and hematopoietic cells, and consequently, bcl-x-deficient mice die around Day 13.5 of embryogenesis. Furthermore, adult bcl-x(+/-) heterozygous male mice have reduced fertility because of testicular degeneration. Bax, a multi-BH (Bcl-2 homology) domain proapoptotic member of the Bcl-2 family, is regulated by BCl-x(L) and is required for the neuropathological abnormalities seen in bcl-x-deficient embryos. The BH3 domain only subgroup of the Bcl-2 family includes proapoptotic members that are essential for the initiation of apoptotic signaling. In this study, we investigated the role for Bim, a BH3 domain only protein, in the embryonic lethality and increased developmental cell death in bcl-x-deficient animals and the perturbed testicular function in bcl-x(+/-) adults. Our studies show that bim deficiency attenuates hematopoietic cell death in the fetal liver of bcl-x-deficient animals, indicating that Bim contributes to programmed cell death in this cell population. In addition, we found that testicular degeneration of adult bcl-x(+/-) males was rescued by concomitant Bim deficiency. However, concomitant Bim deficiency had no effect on the embryonic lethality and widespread nervous system abnormalities caused by bcl-x deficiency. Our work identifies Bim as an important regulator of bcl-x deficiency-induced cell death during hematopoiesis and testicular development.
Publisher: HISTOCHEMICAL SOC INC
Keywords: FAMILY-MEMBER BIM; NERVOUS-SYSTEM; DEATH; INDUCTION; GROWTH; PUMA; BAX; MOUSE
Publisher's Version: https://doi.org/10.1369/jhc.2008.951749
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-10-01 12:00:00