Defects in regulation of apoptosis in caspase-2-deficient mice.
During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.
Bergeron
L
L
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Perez
G I
GI
Macdonald
G
G
Shi
L
L
Sun
Y
Y
Jurisicova
A
A
Varmuza
S
S
Latham
K E
KE
Flaws
J A
JA
Salter
J C
JC
Hara
H
H
Moskowitz
M A
MA
Li
E
E
Greenberg
A
A
Tilly
J L
JL
Yuan
J
J
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D001483:Base Sequence; D001930:Brain Injuries / Q000201:enzymology; D002545:Brain Ischemia / Q000201:enzymology; D053143:Caspase 2; D020169:Caspases; D017931:DNA Primers / Q000235:genetics; D005260:Female; D053804:Granzymes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D009865:Oocytes / Q000166:cytology / Q000201:enzymology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D017931:DNA Primers; D011506:Proteins; D019014:fas Receptor; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; D053143:Caspase 2; D020169:Caspases