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Volume 17, Number 9,
Issue of May 1, 1997
pp. 3112-3119
Copyright ©1997 Society for Neuroscience
bax Deficiency Prevents the Increased Cell Death of
Immature Neurons in bcl-x-Deficient Mice
Received Dec. 19, 1996; revised Feb. 18, 1997; accepted Feb. 20, 1997.
Kenneth S. Shindler1,
Cecelia B. Latham1, and
Kevin A. Roth1, 2
Departments of 1 Pathology and 2 Molecular
Biology and Pharmacology, Washington University School of Medicine, St.
Louis, Missouri 63110
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.
Key words:
apoptosis;
programmed cell death;
bcl-x;
bax;
bcl-2;
development
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