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 phenotypic abnormalities. As presented here, bak(-/-) mice were found to be developmentally normal and reproductively fit and failed to develop any age-related disorders. However, when Bak-deficient mice were mated to Bax-deficient mice to create mice lacking both genes, the majority of bax(-/-)bak(-/-) animals died perinatally with fewer than 10% surviving into adulthood. bax(-/-)bak(-/-) mice displayed multiple developmental defects, including persistence of interdigital webs, an imperforate vaginal canal, and accumulation of excess cells within both the central nervous and hematopoietic systems. Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis.
Lindsten
T
T
Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ross
A J
AJ
King
A
A
Zong
W X
WX
Rathmell
J C
JC
Shiels
H A
HA
Ulrich
E
E
Waymire
K G
KG
Mahar
P
P
Frauwirth
K
K
Chen
Y
Y
Wei
M
M
Eng
V M
VM
Adelman
D M
DM
Simon
M C
MC
Ma
A
A
Golden
J A
JA
Evan
G
G
Korsmeyer
S J
SJ
MacGregor
G R
GR
Thompson
C B
CB
D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001921:Brain / Q000002:abnormalities; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D020043:Genes, Essential / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D007668:Kidney / Q000002:abnormalities / Q000473:pathology; D008221:Lymphoid Tissue / Q000002:abnormalities / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000002:abnormalities / Q000473:pathology; D013950:Thymus Gland / Q000002:abnormalities / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000502:physiology
C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D005047:Etoposide