Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice.
The intracellular balance between pro- and antiapoptotic members of the Bcl-2 gene family is thought to regulate cell death. Targeted disruption of bcl-x, a death repressing member, causes massive cell death of immature neurons in the developing mouse CNS, whereas targeted disruption of bax, a proapoptotic member, blocks the death of specific populations of sympathetic and motor neurons. In the present study, mice deficient in both Bcl-xL and Bax (bcl-x-/-/bax-/-) are used to examine the relative significance and potential interactions of Bcl-xL and Bax during early CNS development. bcl-x-/-/bax-/- mice demonstrate greatly reduced levels of apoptosis both in vivo and in vitro compared with the CNS of Bcl-xL-deficient mice, as assessed by histology and terminal deoxytransferase-mediated deoxyuridine triphosphate nick end-labeling. Bax-deficient mice, however, contain occasional apoptotic cells in the developing CNS, and cultures of bax-deficient telencephalic cells demonstrate similar levels of apoptosis as wild-type cultures. These results suggest that Bax critically interacts with Bcl-xL to regulate survival of immature neurons, but indicate that other cell death regulating proteins, in addition to Bcl-xL and Bax, also function during CNS development.
Shindler
K S
KS
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Latham
C B
CB
Roth
K A
KA
D000818:Animals; D016923:Cell Death / Q000235:genetics*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein