PMID:11784036

Citation	Ross, AJ, Amy, SP, Mahar, PL, Lindsten, T, Knudson, CM, Thompson, CB, Korsmeyer, SJ and MacGregor, GR (2001) BCLW mediates survival of postmitotic Sertoli cells by regulating BAX activity. Dev. Biol. 239:295-308
Abstract	Male mice deficient in BCLW, a death-protecting member of the BCL2 family, are sterile due to an arrest in spermatogenesis that is associated with a gradual loss of germ cells and Sertoli cells from the testis. As Bclw is expressed in both Sertoli cells and diploid male germ cells, it has been unclear which of these cell types requires BCLW in a cell-autonomous manner for survival. To determine whether death of Sertoli cells in Bclw mutants is influenced by the protracted loss of germ cells, we examined testes from Bclw/c-kit double mutant mice, which lack germ cells from birth. Loss of BCLW-deficient Sertoli cells occurs in the absence of germ cells, indicating that germ cell death is not required to mediate loss of Sertoli cells in BCLW-deficient mice. This suggests that Sertoli cells require BCLW in a cell-intrinsic manner for long-term survival. The loss of Sertoli cells in Bclw mutants commences shortly after Sertoli cells have become postmitotic. In situ hybridization analysis indicates that Bclw is expressed in Sertoli cells both before and after exit from mitosis. Therefore, Bclw-independent pathways promote the survival of undifferentiated, mitotic Sertoli cells. We show that BAX and BAK, two closely related death-promoting members of the BCL2 family, are expressed in Sertoli cells. To determine whether either BAX or BAK activity is required for Sertoli cell death in Bclw mutant animals, we analyzed survival of Sertoli cells in Bclw/Bax and Bclw/Bak double homozygous mutant mice. While mutation of Bak had no effect, ablation of Bax suppressed the loss of Sertoli cells in Bclw mutants. Thus, BCLW mediates survival of postmitotic Sertoli cells in the mouse by suppressing death-promoting activity of BAX.
Links	PubMed Online version:10.1006/dbio.2001.0445
Keywords	Animals; Blotting, Western; Cell Death; Cell Survival; Down-Regulation; Genotype; Germ Cells; Homozygote; Immunoblotting; Immunohistochemistry; In Situ Hybridization; Leydig Cells/cytology; Leydig Cells/metabolism; Male; Mice; Mitosis; Mutation; Proteins; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Proto-Oncogene Proteins c-bcl-2/physiology; Sertoli Cells/cytology; Sertoli Cells/metabolism; Testis/metabolism; Testis/pathology; Time Factors; bcl-2-Associated X Protein
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