Bax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death

Abstract

BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…correct Sertoli/germ cell‐ratio for the successive rounds of spermatogenesis is established during the first wave of spermatogenesis (Shaha et al ., 2010). Important effectors of the first‐wave apoptosis are the pro‐apoptotic Bax and anti‐apoptotic Bcl‐w, Bcl‐X L and Bcl‐2 (Knudson et al ., 1995; Furuchi et al ., 1996; Rodriguez et al ., 1997; Yan et al ., 2003; Jahnukainen et al ., 2004). Ablation of Bax or over‐expression of the anti‐apoptotic factors (Bcl‐2 or Bcl‐X L ) result in disruption of spermatogenesis because of eliminated first‐wave apoptosis.…”

BH3-only proteins and their roles in programmed cell death

“…These two pro-apoptotic proteins contain BH1-3 domains, and have a 3D structure very similar to that of the pro-survival members of the family (Sattler et al, 1997;Suzuki et al, 2000;Moldoveanu et al, 2006). Mice lacking Bax show mild lymphoid hyperplasia and male sterility because of sperm-cell differentiation defects (Knudson et al, 1995). Mice lacking Bak have no documented defect so far.…”

The impact of bcl-2 expression and bax deficiency on prostate homeostasis in vivo

“…The bax 7/7 knockout mice (Knudson et al, 1995) were generously provided by Dr Stanley Korsmeyer (Harvard Medical School, Boston, MA, USA) and the genotypes determined by PCR screening with oligonucleotides speci®c for the bax construct as described (Knudson and Korsmeyer, 1997).…”

“…We used the probasin promoter to target expression of a human bcl-2 transgene speci®-cally to the prostate in order to assess its impact on conferring resistance to androgen withdrawal in prostatic glandular epithelial cells in vivo. Additionally, we examined the contribution of bax to mediating androgen-responsiveness in prostatic glandular epithelial cells using bax knockout mice (Knudson et al, 1995).…”