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

TLDR

BAX, a heterodimeric partner of BCL2, counteracts BCL2 and promotes apoptosis in gain‑of‑function studies. A Bax knockout mouse was generated that proved viable yet exhibited lineage‑specific aberrations in cell death. Bax deficiency causes lineage‑specific cell‑death abnormalities, leading to thymocyte and B‑cell hyperplasia, abnormal ovarian follicles, male infertility from disordered seminiferous tubules lacking mature sperm, and widespread multinucleated and dysplastic cells, illustrating that Bax loss induces hyperplasia or hypoplasia depending on cellular context.

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.