The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues

Proapoptotic Bcl-2 family members have been proposed to play a central role in regulating apoptosis. However, mice lacking bax display limited phenoty pic abnormalities. As presented here, bak(-/-) mice were found to be develo pmentally normal and reproductively fit and failed to develop any age-relat ed disorders. However, when Bak-deficient mice were mated to Bax-deficient mice to create mice lacking both genes, the majority of bax(-/-)bak(-/-) an imals died perinatally with fewer than 10% surviving into adulthood. bax(-/ -)bak(-/-) mice displayed multiple developmental defects, including persist ence of interdigital webs, an imperforate vaginal canal, and accumulation o f excess cells within both the central nervous and hematopoietic systems. T hus, Bax and Bak have overlapping roles in the regulation of apoptosis duri ng mammalian development and tissue homeostasis.