BCLW Mediates Survival of Postmitotic Sertoli Cells by Regulating BAX Activity

التفاصيل البيبلوغرافية
العنوان: BCLW Mediates Survival of Postmitotic Sertoli Cells by Regulating BAX Activity
المؤلفون: Ross, Andrea J., Amy, Scott P., Mahar, Patryce L., Lindsten, Tullia, Knudson, C.Michael, Thompson, Craig B., Korsmeyer, Stanley J., MacGregor, Grant R.
المصدر: Developmental Biology; November 2001, Vol. 239 Issue: 2 p295-308, 14p
مستخلص: 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 Bclwis 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 Bclwmutants is influenced by the protracted loss of germ cells, we examined testes from Bclw/c-kitdouble 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 Bclwmutants commences shortly after Sertoli cells have become postmitotic. In situhybridization analysis indicates that Bclwis 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 Bclwmutant animals, we analyzed survival of Sertoli cells in Bclw/Baxand Bclw/Bakdouble homozygous mutant mice. While mutation of Bakhad no effect, ablation of Baxsuppressed the loss of Sertoli cells in Bclwmutants. Thus, BCLW mediates survival of postmitotic Sertoli cells in the mouse by suppressing death-promoting activity of BAX.
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