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

Rizwan S. Akhtar, Barbara J. Klocke, Andreas Strasser, Kevin A. Roth

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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-xL 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-xL 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.

Original languageEnglish (US)
Pages (from-to)921-927
Number of pages7
JournalJournal of Histochemistry and Cytochemistry
Volume56
Issue number10
DOIs
StatePublished - Oct 2008

Keywords

  • Apoptosis
  • Bcl-2
  • Bim
  • Hematopoiesis
  • Neurodegeneration
  • Testicular development

ASJC Scopus subject areas

  • Anatomy
  • Histology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this