Some mice lacking intrinsic, as well as death receptor induced apoptosis and necroptosis, can survive to adulthood.

Programmed cell death, in particular the intrinsic apoptotic pathway, has been shown to play a critical role in the shaping of tissues during embryonic development. The multi-BCL-2 Homology (BH) domain effectors of apoptosis, BAX, BAK, and BOK, are essential for cell killing in the intrinsic apoptotic pathway. It was therefore surprising that we found earlier that a few mice lacking all effectors of apoptosis ( triple knockout), albeit many fewer than expected based on Mendelian ratios, could reach weaning or even adulthood.

Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK.

Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, BokBaxBak animals exhibited more severe defects and died earlier than BaxBak mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death.